VCV000054172.21 - ClinVar

NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(10)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(4)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)

Variation ID: 54172 Accession: VCV000054172.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43115736 (GRCh38) [ NCBI UCSC ] 17: 41267753 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 1, 2014	May 1, 2024	Jun 8, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.124A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.Ile42Val	missense
NM_001407571.1:c.-65A>G
NM_001407581.1:c.124A>G	NP_001394510.1:p.Ile42Val	missense
NM_001407582.1:c.124A>G	NP_001394511.1:p.Ile42Val	missense
NM_001407583.1:c.124A>G	NP_001394512.1:p.Ile42Val	missense
NM_001407585.1:c.124A>G	NP_001394514.1:p.Ile42Val	missense
NM_001407587.1:c.124A>G	NP_001394516.1:p.Ile42Val	missense
NM_001407590.1:c.124A>G	NP_001394519.1:p.Ile42Val	missense
NM_001407591.1:c.124A>G	NP_001394520.1:p.Ile42Val	missense
NM_001407593.1:c.124A>G	NP_001394522.1:p.Ile42Val	missense
NM_001407594.1:c.124A>G	NP_001394523.1:p.Ile42Val	missense
NM_001407596.1:c.124A>G	NP_001394525.1:p.Ile42Val	missense
NM_001407597.1:c.124A>G	NP_001394526.1:p.Ile42Val	missense
NM_001407598.1:c.124A>G	NP_001394527.1:p.Ile42Val	missense
NM_001407602.1:c.124A>G	NP_001394531.1:p.Ile42Val	missense
NM_001407603.1:c.124A>G	NP_001394532.1:p.Ile42Val	missense
NM_001407605.1:c.124A>G	NP_001394534.1:p.Ile42Val	missense
NM_001407610.1:c.124A>G	NP_001394539.1:p.Ile42Val	missense
NM_001407611.1:c.124A>G	NP_001394540.1:p.Ile42Val	missense
NM_001407612.1:c.124A>G	NP_001394541.1:p.Ile42Val	missense
NM_001407613.1:c.124A>G	NP_001394542.1:p.Ile42Val	missense
NM_001407614.1:c.124A>G	NP_001394543.1:p.Ile42Val	missense
NM_001407615.1:c.124A>G	NP_001394544.1:p.Ile42Val	missense
NM_001407616.1:c.124A>G	NP_001394545.1:p.Ile42Val	missense
NM_001407617.1:c.124A>G	NP_001394546.1:p.Ile42Val	missense
NM_001407618.1:c.124A>G	NP_001394547.1:p.Ile42Val	missense
NM_001407619.1:c.124A>G	NP_001394548.1:p.Ile42Val	missense
NM_001407620.1:c.124A>G	NP_001394549.1:p.Ile42Val	missense
NM_001407621.1:c.124A>G	NP_001394550.1:p.Ile42Val	missense
NM_001407622.1:c.124A>G	NP_001394551.1:p.Ile42Val	missense
NM_001407623.1:c.124A>G	NP_001394552.1:p.Ile42Val	missense
NM_001407624.1:c.124A>G	NP_001394553.1:p.Ile42Val	missense
NM_001407625.1:c.124A>G	NP_001394554.1:p.Ile42Val	missense
NM_001407626.1:c.124A>G	NP_001394555.1:p.Ile42Val	missense
NM_001407627.1:c.124A>G	NP_001394556.1:p.Ile42Val	missense
NM_001407628.1:c.124A>G	NP_001394557.1:p.Ile42Val	missense
NM_001407629.1:c.124A>G	NP_001394558.1:p.Ile42Val	missense
NM_001407630.1:c.124A>G	NP_001394559.1:p.Ile42Val	missense
NM_001407631.1:c.124A>G	NP_001394560.1:p.Ile42Val	missense
NM_001407632.1:c.124A>G	NP_001394561.1:p.Ile42Val	missense
NM_001407633.1:c.124A>G	NP_001394562.1:p.Ile42Val	missense
NM_001407634.1:c.124A>G	NP_001394563.1:p.Ile42Val	missense
NM_001407635.1:c.124A>G	NP_001394564.1:p.Ile42Val	missense
NM_001407636.1:c.124A>G	NP_001394565.1:p.Ile42Val	missense
NM_001407637.1:c.124A>G	NP_001394566.1:p.Ile42Val	missense
NM_001407638.1:c.124A>G	NP_001394567.1:p.Ile42Val	missense
NM_001407639.1:c.124A>G	NP_001394568.1:p.Ile42Val	missense
NM_001407640.1:c.124A>G	NP_001394569.1:p.Ile42Val	missense
NM_001407641.1:c.124A>G	NP_001394570.1:p.Ile42Val	missense
NM_001407642.1:c.124A>G	NP_001394571.1:p.Ile42Val	missense
NM_001407644.1:c.124A>G	NP_001394573.1:p.Ile42Val	missense
NM_001407645.1:c.124A>G	NP_001394574.1:p.Ile42Val	missense
NM_001407646.1:c.124A>G	NP_001394575.1:p.Ile42Val	missense
NM_001407647.1:c.124A>G	NP_001394576.1:p.Ile42Val	missense
NM_001407648.1:c.124A>G	NP_001394577.1:p.Ile42Val	missense
NM_001407649.1:c.124A>G	NP_001394578.1:p.Ile42Val	missense
NM_001407652.1:c.124A>G	NP_001394581.1:p.Ile42Val	missense
NM_001407653.1:c.124A>G	NP_001394582.1:p.Ile42Val	missense
NM_001407654.1:c.124A>G	NP_001394583.1:p.Ile42Val	missense
NM_001407655.1:c.124A>G	NP_001394584.1:p.Ile42Val	missense
NM_001407656.1:c.124A>G	NP_001394585.1:p.Ile42Val	missense
NM_001407657.1:c.124A>G	NP_001394586.1:p.Ile42Val	missense
NM_001407658.1:c.124A>G	NP_001394587.1:p.Ile42Val	missense
NM_001407659.1:c.124A>G	NP_001394588.1:p.Ile42Val	missense
NM_001407660.1:c.124A>G	NP_001394589.1:p.Ile42Val	missense
NM_001407661.1:c.124A>G	NP_001394590.1:p.Ile42Val	missense
NM_001407662.1:c.124A>G	NP_001394591.1:p.Ile42Val	missense
NM_001407663.1:c.124A>G	NP_001394592.1:p.Ile42Val	missense
NM_001407664.1:c.124A>G	NP_001394593.1:p.Ile42Val	missense
NM_001407665.1:c.124A>G	NP_001394594.1:p.Ile42Val	missense
NM_001407666.1:c.124A>G	NP_001394595.1:p.Ile42Val	missense
NM_001407667.1:c.124A>G	NP_001394596.1:p.Ile42Val	missense
NM_001407668.1:c.124A>G	NP_001394597.1:p.Ile42Val	missense
NM_001407669.1:c.124A>G	NP_001394598.1:p.Ile42Val	missense
NM_001407670.1:c.124A>G	NP_001394599.1:p.Ile42Val	missense
NM_001407671.1:c.124A>G	NP_001394600.1:p.Ile42Val	missense
NM_001407672.1:c.124A>G	NP_001394601.1:p.Ile42Val	missense
NM_001407673.1:c.124A>G	NP_001394602.1:p.Ile42Val	missense
NM_001407674.1:c.124A>G	NP_001394603.1:p.Ile42Val	missense
NM_001407675.1:c.124A>G	NP_001394604.1:p.Ile42Val	missense
NM_001407676.1:c.124A>G	NP_001394605.1:p.Ile42Val	missense
NM_001407677.1:c.124A>G	NP_001394606.1:p.Ile42Val	missense
NM_001407678.1:c.124A>G	NP_001394607.1:p.Ile42Val	missense
NM_001407679.1:c.124A>G	NP_001394608.1:p.Ile42Val	missense
NM_001407680.1:c.124A>G	NP_001394609.1:p.Ile42Val	missense
NM_001407681.1:c.124A>G	NP_001394610.1:p.Ile42Val	missense
NM_001407682.1:c.124A>G	NP_001394611.1:p.Ile42Val	missense
NM_001407683.1:c.124A>G	NP_001394612.1:p.Ile42Val	missense
NM_001407684.1:c.124A>G	NP_001394613.1:p.Ile42Val	missense
NM_001407685.1:c.124A>G	NP_001394614.1:p.Ile42Val	missense
NM_001407686.1:c.124A>G	NP_001394615.1:p.Ile42Val	missense
NM_001407687.1:c.124A>G	NP_001394616.1:p.Ile42Val	missense
NM_001407688.1:c.124A>G	NP_001394617.1:p.Ile42Val	missense
NM_001407689.1:c.124A>G	NP_001394618.1:p.Ile42Val	missense
NM_001407690.1:c.124A>G	NP_001394619.1:p.Ile42Val	missense
NM_001407691.1:c.124A>G	NP_001394620.1:p.Ile42Val	missense
NM_001407694.1:c.-134A>G
NM_001407695.1:c.-138A>G
NM_001407696.1:c.-134A>G
NM_001407697.1:c.-18A>G
NM_001407724.1:c.-134A>G
NM_001407725.1:c.-18A>G
NM_001407727.1:c.-134A>G
NM_001407728.1:c.-18A>G
NM_001407729.1:c.-18A>G
NM_001407730.1:c.-18A>G
NM_001407731.1:c.-134A>G
NM_001407733.1:c.-134A>G
NM_001407734.1:c.-18A>G
NM_001407735.1:c.-18A>G
NM_001407737.1:c.-18A>G
NM_001407739.1:c.-18A>G
NM_001407740.1:c.-18A>G
NM_001407741.1:c.-18A>G
NM_001407743.1:c.-18A>G
NM_001407745.1:c.-18A>G
NM_001407746.1:c.-134A>G
NM_001407748.1:c.-18A>G
NM_001407749.1:c.-134A>G
NM_001407752.1:c.-18A>G
NM_001407838.1:c.-18A>G
NM_001407839.1:c.-18A>G
NM_001407841.1:c.-14A>G
NM_001407842.1:c.-134A>G
NM_001407843.1:c.-134A>G
NM_001407844.1:c.-18A>G
NM_001407846.1:c.-18A>G
NM_001407847.1:c.-18A>G
NM_001407848.1:c.-18A>G
NM_001407850.1:c.-18A>G
NM_001407851.1:c.-18A>G
NM_001407853.1:c.-65A>G
NM_001407854.1:c.124A>G	NP_001394783.1:p.Ile42Val	missense
NM_001407858.1:c.124A>G	NP_001394787.1:p.Ile42Val	missense
NM_001407859.1:c.124A>G	NP_001394788.1:p.Ile42Val	missense
NM_001407860.1:c.124A>G	NP_001394789.1:p.Ile42Val	missense
NM_001407861.1:c.124A>G	NP_001394790.1:p.Ile42Val	missense
NM_001407862.1:c.124A>G	NP_001394791.1:p.Ile42Val	missense
NM_001407863.1:c.124A>G	NP_001394792.1:p.Ile42Val	missense
NM_001407874.1:c.124A>G	NP_001394803.1:p.Ile42Val	missense
NM_001407875.1:c.124A>G	NP_001394804.1:p.Ile42Val	missense
NM_001407879.1:c.-65A>G
NM_001407882.1:c.-65A>G
NM_001407884.1:c.-65A>G
NM_001407885.1:c.-65A>G
NM_001407886.1:c.-65A>G
NM_001407887.1:c.-65A>G
NM_001407889.1:c.-181A>G
NM_001407894.1:c.-65A>G
NM_001407895.1:c.-65A>G
NM_001407896.1:c.-65A>G
NM_001407897.1:c.-65A>G
NM_001407899.1:c.-65A>G
NM_001407900.1:c.-181A>G
NM_001407904.1:c.-65A>G
NM_001407906.1:c.-65A>G
NM_001407907.1:c.-65A>G
NM_001407908.1:c.-65A>G
NM_001407909.1:c.-65A>G
NM_001407910.1:c.-65A>G
NM_001407915.1:c.-65A>G
NM_001407916.1:c.-65A>G
NM_001407917.1:c.-65A>G
NM_001407918.1:c.-65A>G
NM_001407919.1:c.124A>G	NP_001394848.1:p.Ile42Val	missense
NM_001407920.1:c.-18A>G
NM_001407921.1:c.-18A>G
NM_001407922.1:c.-18A>G
NM_001407923.1:c.-18A>G
NM_001407926.1:c.-18A>G
NM_001407927.1:c.-18A>G
NM_001407930.1:c.-134A>G
NM_001407933.1:c.-18A>G
NM_001407934.1:c.-18A>G
NM_001407935.1:c.-18A>G
NM_001407937.1:c.124A>G	NP_001394866.1:p.Ile42Val	missense
NM_001407938.1:c.124A>G	NP_001394867.1:p.Ile42Val	missense
NM_001407939.1:c.124A>G	NP_001394868.1:p.Ile42Val	missense
NM_001407940.1:c.124A>G	NP_001394869.1:p.Ile42Val	missense
NM_001407941.1:c.124A>G	NP_001394870.1:p.Ile42Val	missense
NM_001407942.1:c.-134A>G
NM_001407943.1:c.-18A>G
NM_001407944.1:c.-18A>G
NM_001407946.1:c.-65A>G
NM_001407947.1:c.-65A>G
NM_001407948.1:c.-65A>G
NM_001407949.1:c.-65A>G
NM_001407950.1:c.-65A>G
NM_001407951.1:c.-65A>G
NM_001407952.1:c.-65A>G
NM_001407953.1:c.-65A>G
NM_001407954.1:c.-65A>G
NM_001407955.1:c.-65A>G
NM_001407956.1:c.-65A>G
NM_001407957.1:c.-65A>G
NM_001407958.1:c.-65A>G
NM_001407960.1:c.-180A>G
NM_001407962.1:c.-180A>G
NM_001407964.1:c.-18A>G
NM_001407965.1:c.-296A>G
NM_001407968.1:c.124A>G	NP_001394897.1:p.Ile42Val	missense
NM_001407969.1:c.124A>G	NP_001394898.1:p.Ile42Val	missense
NM_001407970.1:c.124A>G	NP_001394899.1:p.Ile42Val	missense
NM_001407971.1:c.124A>G	NP_001394900.1:p.Ile42Val	missense
NM_001407972.1:c.124A>G	NP_001394901.1:p.Ile42Val	missense
NM_001407973.1:c.124A>G	NP_001394902.1:p.Ile42Val	missense
NM_001407974.1:c.124A>G	NP_001394903.1:p.Ile42Val	missense
NM_001407975.1:c.124A>G	NP_001394904.1:p.Ile42Val	missense
NM_001407976.1:c.124A>G	NP_001394905.1:p.Ile42Val	missense
NM_001407977.1:c.124A>G	NP_001394906.1:p.Ile42Val	missense
NM_001407978.1:c.124A>G	NP_001394907.1:p.Ile42Val	missense
NM_001407979.1:c.124A>G	NP_001394908.1:p.Ile42Val	missense
NM_001407980.1:c.124A>G	NP_001394909.1:p.Ile42Val	missense
NM_001407981.1:c.124A>G	NP_001394910.1:p.Ile42Val	missense
NM_001407982.1:c.124A>G	NP_001394911.1:p.Ile42Val	missense
NM_001407983.1:c.124A>G	NP_001394912.1:p.Ile42Val	missense
NM_001407984.1:c.124A>G	NP_001394913.1:p.Ile42Val	missense
NM_001407985.1:c.124A>G	NP_001394914.1:p.Ile42Val	missense
NM_001407986.1:c.124A>G	NP_001394915.1:p.Ile42Val	missense
NM_001407990.1:c.124A>G	NP_001394919.1:p.Ile42Val	missense
NM_001407991.1:c.124A>G	NP_001394920.1:p.Ile42Val	missense
NM_001407992.1:c.124A>G	NP_001394921.1:p.Ile42Val	missense
NM_001407993.1:c.124A>G	NP_001394922.1:p.Ile42Val	missense
NM_001408392.1:c.124A>G	NP_001395321.1:p.Ile42Val	missense
NM_001408396.1:c.124A>G	NP_001395325.1:p.Ile42Val	missense
NM_001408397.1:c.124A>G	NP_001395326.1:p.Ile42Val	missense
NM_001408398.1:c.124A>G	NP_001395327.1:p.Ile42Val	missense
NM_001408399.1:c.124A>G	NP_001395328.1:p.Ile42Val	missense
NM_001408400.1:c.124A>G	NP_001395329.1:p.Ile42Val	missense
NM_001408401.1:c.124A>G	NP_001395330.1:p.Ile42Val	missense
NM_001408402.1:c.124A>G	NP_001395331.1:p.Ile42Val	missense
NM_001408403.1:c.124A>G	NP_001395332.1:p.Ile42Val	missense
NM_001408404.1:c.124A>G	NP_001395333.1:p.Ile42Val	missense
NM_001408406.1:c.124A>G	NP_001395335.1:p.Ile42Val	missense
NM_001408407.1:c.124A>G	NP_001395336.1:p.Ile42Val	missense
NM_001408408.1:c.124A>G	NP_001395337.1:p.Ile42Val	missense
NM_001408409.1:c.124A>G	NP_001395338.1:p.Ile42Val	missense
NM_001408410.1:c.-18A>G
NM_001408411.1:c.124A>G	NP_001395340.1:p.Ile42Val	missense
NM_001408412.1:c.124A>G	NP_001395341.1:p.Ile42Val	missense
NM_001408413.1:c.124A>G	NP_001395342.1:p.Ile42Val	missense
NM_001408414.1:c.124A>G	NP_001395343.1:p.Ile42Val	missense
NM_001408415.1:c.124A>G	NP_001395344.1:p.Ile42Val	missense
NM_001408416.1:c.124A>G	NP_001395345.1:p.Ile42Val	missense
NM_001408418.1:c.124A>G	NP_001395347.1:p.Ile42Val	missense
NM_001408419.1:c.124A>G	NP_001395348.1:p.Ile42Val	missense
NM_001408420.1:c.124A>G	NP_001395349.1:p.Ile42Val	missense
NM_001408421.1:c.124A>G	NP_001395350.1:p.Ile42Val	missense
NM_001408422.1:c.124A>G	NP_001395351.1:p.Ile42Val	missense
NM_001408423.1:c.124A>G	NP_001395352.1:p.Ile42Val	missense
NM_001408424.1:c.124A>G	NP_001395353.1:p.Ile42Val	missense
NM_001408425.1:c.124A>G	NP_001395354.1:p.Ile42Val	missense
NM_001408426.1:c.124A>G	NP_001395355.1:p.Ile42Val	missense
NM_001408427.1:c.124A>G	NP_001395356.1:p.Ile42Val	missense
NM_001408428.1:c.124A>G	NP_001395357.1:p.Ile42Val	missense
NM_001408429.1:c.124A>G	NP_001395358.1:p.Ile42Val	missense
NM_001408430.1:c.124A>G	NP_001395359.1:p.Ile42Val	missense
NM_001408431.1:c.124A>G	NP_001395360.1:p.Ile42Val	missense
NM_001408432.1:c.124A>G	NP_001395361.1:p.Ile42Val	missense
NM_001408433.1:c.124A>G	NP_001395362.1:p.Ile42Val	missense
NM_001408434.1:c.124A>G	NP_001395363.1:p.Ile42Val	missense
NM_001408435.1:c.124A>G	NP_001395364.1:p.Ile42Val	missense
NM_001408436.1:c.124A>G	NP_001395365.1:p.Ile42Val	missense
NM_001408437.1:c.124A>G	NP_001395366.1:p.Ile42Val	missense
NM_001408438.1:c.124A>G	NP_001395367.1:p.Ile42Val	missense
NM_001408439.1:c.124A>G	NP_001395368.1:p.Ile42Val	missense
NM_001408440.1:c.124A>G	NP_001395369.1:p.Ile42Val	missense
NM_001408441.1:c.124A>G	NP_001395370.1:p.Ile42Val	missense
NM_001408442.1:c.124A>G	NP_001395371.1:p.Ile42Val	missense
NM_001408443.1:c.124A>G	NP_001395372.1:p.Ile42Val	missense
NM_001408444.1:c.124A>G	NP_001395373.1:p.Ile42Val	missense
NM_001408445.1:c.124A>G	NP_001395374.1:p.Ile42Val	missense
NM_001408446.1:c.124A>G	NP_001395375.1:p.Ile42Val	missense
NM_001408447.1:c.124A>G	NP_001395376.1:p.Ile42Val	missense
NM_001408448.1:c.124A>G	NP_001395377.1:p.Ile42Val	missense
NM_001408450.1:c.124A>G	NP_001395379.1:p.Ile42Val	missense
NM_001408452.1:c.-18A>G
NM_001408453.1:c.-18A>G
NM_001408455.1:c.-134A>G
NM_001408456.1:c.-134A>G
NM_001408458.1:c.-18A>G
NM_001408462.1:c.-18A>G
NM_001408463.1:c.-18A>G
NM_001408465.1:c.-138A>G
NM_001408466.1:c.-18A>G
NM_001408468.1:c.-134A>G
NM_001408469.1:c.-18A>G
NM_001408470.1:c.-18A>G
NM_001408472.1:c.124A>G	NP_001395401.1:p.Ile42Val	missense
NM_001408473.1:c.124A>G	NP_001395402.1:p.Ile42Val	missense
NM_001408474.1:c.124A>G	NP_001395403.1:p.Ile42Val	missense
NM_001408475.1:c.124A>G	NP_001395404.1:p.Ile42Val	missense
NM_001408476.1:c.124A>G	NP_001395405.1:p.Ile42Val	missense
NM_001408478.1:c.-65A>G
NM_001408479.1:c.-65A>G
NM_001408480.1:c.-65A>G
NM_001408481.1:c.-65A>G
NM_001408482.1:c.-65A>G
NM_001408483.1:c.-65A>G
NM_001408484.1:c.-65A>G
NM_001408485.1:c.-65A>G
NM_001408489.1:c.-65A>G
NM_001408490.1:c.-65A>G
NM_001408491.1:c.-65A>G
NM_001408492.1:c.-181A>G
NM_001408493.1:c.-65A>G
NM_001408494.1:c.124A>G	NP_001395423.1:p.Ile42Val	missense
NM_001408495.1:c.124A>G	NP_001395424.1:p.Ile42Val	missense
NM_001408497.1:c.-18A>G
NM_001408499.1:c.-18A>G
NM_001408500.1:c.-18A>G
NM_001408501.1:c.-134A>G
NM_001408502.1:c.-65A>G
NM_001408503.1:c.-18A>G
NM_001408504.1:c.-18A>G
NM_001408505.1:c.-18A>G
NM_001408506.1:c.-65A>G
NM_001408507.1:c.-65A>G
NM_001408508.1:c.-65A>G
NM_001408509.1:c.-65A>G
NM_001408510.1:c.-180A>G
NM_001408512.1:c.-180A>G
NM_001408513.1:c.-65A>G
NM_001408514.1:c.-65A>G
NM_007297.4:c.-8+8281A>G		intron variant
NM_007298.4:c.124A>G	NP_009229.2:p.Ile42Val	missense
NM_007299.4:c.124A>G	NP_009230.2:p.Ile42Val	missense
NM_007300.4:c.124A>G	NP_009231.2:p.Ile42Val	missense
NM_007304.2:c.124A>G	NP_009235.2:p.Ile42Val	missense
NR_027676.2:n.326A>G		non-coding transcript variant
NC_000017.11:g.43115736T>C
NC_000017.10:g.41267753T>C
NG_005905.2:g.102248A>G
LRG_292:g.102248A>G
LRG_292t1:c.124A>G	LRG_292p1:p.Ile42Val
U14680.1:n.243A>G

... more HGVS ... less HGVS

Protein change

I42V

Other names

Canonical SPDI

NC_000017.11:43115735:T:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

functionally_normal; Sequence Ontology [ SO:0002219]

The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.124A>G, a MISSENSE variant, produced a function score of 0.11, corresponding to a functional classification of FUNCTIONAL. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00000

Links

ClinGen: CA000820 dbSNP: rs80357163 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRCA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	13041	14847

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Breast-ovarian cancer, familial, susceptibility to, 1	Conflicting interpretations of pathogenicity (5)	criteria provided, conflicting classifications	Jun 8, 2023	RCV000083167.17
Hereditary cancer-predisposing syndrome	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	May 16, 2023	RCV000775195.15
not specified	Likely benign (1)	criteria provided, single submitter	Jun 8, 2023	RCV001175357.10
Hereditary breast ovarian cancer syndrome	Likely benign (1)	criteria provided, single submitter	Sep 1, 2022	RCV001398773.16
not provided	Uncertain significance (1)	criteria provided, single submitter	Feb 16, 2023	RCV003476945.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Apr 03, 2023)	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Myriad Genetics, Inc. Accession: SCV004019715.1 First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023	Publications: PubMed (1) PubMed: 25085752 Comment: This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic … (more) This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. (less)
Likely benign (May 05, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002674518.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (11) PubMed: 11320250‚ 16403807‚ 20103620‚ 21725363‚ 23161852‚ 24289923‚ 24411079‚ 25823446‚ 30209399‚ 30219179‚ 30696104 Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (Sep 01, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001600548.4 First in ClinVar: May 16, 2021 Last updated: Apr 09, 2023
Likely benign (Jun 08, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000698840.3 First in ClinVar: Mar 17, 2018 Last updated: Jul 29, 2023	Publications: PubMed (12) PubMed: 15235020‚ 23161852‚ 16403807‚ 20103620‚ 21725363‚ 11320250‚ 25823446‚ 24411079‚ 24289923‚ 30209399‚ 30696104‚ 30219179 Comment: Variant summary: BRCA1 c.124A>G (p.Ile42Val) results in a conservative amino acid change located in the RING-type zinc finger domain (IPR001841) of the encoded protein sequence. … (more) Variant summary: BRCA1 c.124A>G (p.Ile42Val) results in a conservative amino acid change located in the RING-type zinc finger domain (IPR001841) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250738 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.124A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. Multiple studies have shown this variant protein retains normal activity (Ransburgh_2010, Starita_2018, Findlay_2018 Caleca_2019). At least one study showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The following publications have been ascertained in the context of this evaluation (PMID: 15235020, 30696104, 30209399, 24411079, 21725363, 24289923, 16403807, 20103620, 11320250, 30219179, 25823446, 23161852). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. (less)
Uncertain significance (Feb 16, 2023)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV004222555.1 First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024	Publications: PubMed (11) PubMed: 30696104‚ 30219179‚ 30209399‚ 25823446‚ 24289923‚ 23161852‚ 21725363‚ 20103620‚ 16403807‚ 15235020‚ 11320250 Comment: The frequency of this variant in the general population, 0.00021 (1/4830 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Published functional studies have shown … (more) The frequency of this variant in the general population, 0.00021 (1/4830 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Published functional studies have shown that this variant does not affect the BRCA1 function of DNA double-strand break repair (PMIDs: 30696104 (2018), 30219179 (2018), 30209399 (2018), 25823446 (2015), 23161852 (2013), 11320250 (2001), 15235020 (2004), 21725363 (2012), 20103620 (2010), 16403807 (2006)), but is deficient in the function of regulating centrosome number (PMIDs: 24288923 (2013), 23161852 (2013)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
Uncertain significance (May 16, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000909421.3 First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 11320250‚ 21725363‚ 23161852‚ 30209399‚ 30696104 Comment: This missense variant replaces isoleucine with valine at codon 42 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure … (more) This missense variant replaces isoleucine with valine at codon 42 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in a haploid cell proliferation assay, homology-directed DNA repair, ubiquitin ligase assays and in the rescue of cell survival to ionizing radiation in Brca1-null cells (PMID: 11320250, 21725363, 23161852, 30209399, 30696104). To our knowledge, this variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional clinical studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Uncertain Significance (Jun 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	All of Us Research Program, National Institutes of Health Accession: SCV004823699.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Publications: PubMed (5) PubMed: 11320250‚ 21725363‚ 23161852‚ 30209399‚ 30696104 Comment: This missense variant replaces isoleucine with valine at codon 42 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure … (more) This missense variant replaces isoleucine with valine at codon 42 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in a haploid cell proliferation assay, homology-directed DNA repair, ubiquitin ligase assays and in the rescue of cell survival to ionizing radiation in Brca1-null cells (PMID: 11320250, 21725363, 23161852, 30209399, 30696104). To our knowledge, this variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional clinical studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Number of individuals with the variant: 1
Uncertain significance (Mar 24, 1999)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 1 Affected status: yes Allele origin: germline	Breast Cancer Information Core (BIC) (BRCA1) Accession: SCV000144379.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014	Number of individuals with the variant: 3
Uncertain significance (May 01, 2012)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial 1 Affected status: not provided Allele origin: germline	Sharing Clinical Reports Project (SCRP) Accession: SCV000115241.3 First in ClinVar: Feb 06, 2014 Last updated: Sep 27, 2014
not provided (-)	no classification provided Method: in vitro	Breast-ovarian cancer, familial 1 Affected status: not applicable Allele origin: not applicable	Brotman Baty Institute, University of Washington Accession: SCV001237892.1 First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020	Publications: PubMed (1) PubMed: 30209399 Other databases https://sge.gs.washington.edu/BR… https://sge.gs.washington.edu/BRCA1/ Method: saturation genome editing in haploid cells Result: FUNCTIONAL:0.109884311248167

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

Variant summary: BRCA1 c.124A>G (p.Ile42Val) results in a conservative amino acid change located in the RING-type zinc finger domain (IPR001841) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250738 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.124A>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. Multiple studies have shown this variant protein retains normal activity (Ransburgh_2010, Starita_2018, Findlay_2018 Caleca_2019). At least one study showed no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). HDR assays qualify as a recognized gold standard on the basis of updated guidance provided by the ClinGen Sequence Variant Interpretation (SVI) working group. The following publications have been ascertained in the context of this evaluation (PMID: 15235020, 30696104, 30209399, 24411079, 21725363, 24289923, 16403807, 20103620, 11320250, 30219179, 25823446, 23161852). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign.

Comment:

The frequency of this variant in the general population, 0.00021 (1/4830 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Published functional studies have shown that this variant does not affect the BRCA1 function of DNA double-strand break repair (PMIDs: 30696104 (2018), 30219179 (2018), 30209399 (2018), 25823446 (2015), 23161852 (2013), 11320250 (2001), 15235020 (2004), 21725363 (2012), 20103620 (2010), 16403807 (2006)), but is deficient in the function of regulating centrosome number (PMIDs: 24288923 (2013), 23161852 (2013)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

Comment:

This missense variant replaces isoleucine with valine at codon 42 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in a haploid cell proliferation assay, homology-directed DNA repair, ubiquitin ligase assays and in the rescue of cell survival to ionizing radiation in Brca1-null cells (PMID: 11320250, 21725363, 23161852, 30209399, 30696104). To our knowledge, this variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Although there is a suspicion that this variant may not be associated with disease, additional clinical studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
functionally_normal (SO:0002219)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	FUNCTIONAL:0.109884311248167	Brotman Baty Institute, University of Washington Accession: SCV001237892.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.124A>G, a MISSENSE variant, produced a function score of 0.11, corresponding to a functional classification of FUNCTIONAL. … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.124A>G, a MISSENSE variant, produced a function score of 0.11, corresponding to a functional classification of FUNCTIONAL. SGE function score ranges for classification are as follows: â€˜functionalâ€™, score > -0.748; â€˜intermediateâ€™, -0.748 > score > -1.328; â€˜non-functionalâ€™, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
GFP-Fragment Reassembly Screens for the Functional Characterization of Variants of Uncertain Significance in Protein Interaction Domains of the BRCA1 and BRCA2 Genes.	Caleca L	Cancers	2019	PMID: 30696104
A Multiplex Homology-Directed DNA Repair Assay Reveals the Impact of More Than 1,000 BRCA1 Missense Substitution Variants on Protein Function.	Starita LM	American journal of human genetics	2018	PMID: 30219179
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.	Starita LM	Genetics	2015	PMID: 25823446
Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.	Pruss D	Breast cancer research and treatment	2014	PMID: 25085752
OLA1 in centrosome biology alongside the BRCA1/BARD1 complex: looking beyond centrosomes.	Gomez V	Molecular cell	2014	PMID: 24411079
The BRCA1/BARD1-interacting protein OLA1 functions in centrosome regulation.	Matsuzawa A	Molecular cell	2014	PMID: 24289923
Analysis of BRCA1 variants in double-strand break repair by homologous recombination and single-strand annealing.	Towler WI	Human mutation	2013	PMID: 23161852
Functional differences among BRCA1 missense mutations in the control of centrosome duplication.	Kais Z	Oncogene	2012	PMID: 21725363
Identification of breast tumor mutations in BRCA1 that abolish its function in homologous DNA recombination.	Ransburgh DJ	Cancer research	2010	PMID: 20103620
Genetic analysis of BRCA1 ubiquitin ligase activity and its relationship to breast cancer susceptibility.	Morris JR	Human molecular genetics	2006	PMID: 16403807
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation.	Abkevich V	Journal of medical genetics	2004	PMID: 15235020
Cancer-predisposing mutations within the RING domain of BRCA1: loss of ubiquitin protein ligase activity and protection from radiation hypersensitivity.	Ruffner H	Proceedings of the National Academy of Sciences of the United States of America	2001	PMID: 11320250
https://sge.gs.washington.edu/BRCA1/	-	-	-	-
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Text-mined citations for rs80357163 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.124A>G (p.Ile42Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80357163 ...