VCV000868161.3 - ClinVar

NM_007294.4(BRCA1):c.121C>G (p.His41Asp)

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.

(2)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.121C>G (p.His41Asp)

Variation ID: 868161 Accession: VCV000868161.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43115739 (GRCh38) [ NCBI UCSC ] 17: 41267756 (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 18, 2020	Feb 20, 2024	Dec 29, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.121C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.His41Asp	missense
NM_001407571.1:c.-68C>G
NM_001407581.1:c.121C>G	NP_001394510.1:p.His41Asp	missense
NM_001407582.1:c.121C>G	NP_001394511.1:p.His41Asp	missense
NM_001407583.1:c.121C>G	NP_001394512.1:p.His41Asp	missense
NM_001407585.1:c.121C>G	NP_001394514.1:p.His41Asp	missense
NM_001407587.1:c.121C>G	NP_001394516.1:p.His41Asp	missense
NM_001407590.1:c.121C>G	NP_001394519.1:p.His41Asp	missense
NM_001407591.1:c.121C>G	NP_001394520.1:p.His41Asp	missense
NM_001407593.1:c.121C>G	NP_001394522.1:p.His41Asp	missense
NM_001407594.1:c.121C>G	NP_001394523.1:p.His41Asp	missense
NM_001407596.1:c.121C>G	NP_001394525.1:p.His41Asp	missense
NM_001407597.1:c.121C>G	NP_001394526.1:p.His41Asp	missense
NM_001407598.1:c.121C>G	NP_001394527.1:p.His41Asp	missense
NM_001407602.1:c.121C>G	NP_001394531.1:p.His41Asp	missense
NM_001407603.1:c.121C>G	NP_001394532.1:p.His41Asp	missense
NM_001407605.1:c.121C>G	NP_001394534.1:p.His41Asp	missense
NM_001407610.1:c.121C>G	NP_001394539.1:p.His41Asp	missense
NM_001407611.1:c.121C>G	NP_001394540.1:p.His41Asp	missense
NM_001407612.1:c.121C>G	NP_001394541.1:p.His41Asp	missense
NM_001407613.1:c.121C>G	NP_001394542.1:p.His41Asp	missense
NM_001407614.1:c.121C>G	NP_001394543.1:p.His41Asp	missense
NM_001407615.1:c.121C>G	NP_001394544.1:p.His41Asp	missense
NM_001407616.1:c.121C>G	NP_001394545.1:p.His41Asp	missense
NM_001407617.1:c.121C>G	NP_001394546.1:p.His41Asp	missense
NM_001407618.1:c.121C>G	NP_001394547.1:p.His41Asp	missense
NM_001407619.1:c.121C>G	NP_001394548.1:p.His41Asp	missense
NM_001407620.1:c.121C>G	NP_001394549.1:p.His41Asp	missense
NM_001407621.1:c.121C>G	NP_001394550.1:p.His41Asp	missense
NM_001407622.1:c.121C>G	NP_001394551.1:p.His41Asp	missense
NM_001407623.1:c.121C>G	NP_001394552.1:p.His41Asp	missense
NM_001407624.1:c.121C>G	NP_001394553.1:p.His41Asp	missense
NM_001407625.1:c.121C>G	NP_001394554.1:p.His41Asp	missense
NM_001407626.1:c.121C>G	NP_001394555.1:p.His41Asp	missense
NM_001407627.1:c.121C>G	NP_001394556.1:p.His41Asp	missense
NM_001407628.1:c.121C>G	NP_001394557.1:p.His41Asp	missense
NM_001407629.1:c.121C>G	NP_001394558.1:p.His41Asp	missense
NM_001407630.1:c.121C>G	NP_001394559.1:p.His41Asp	missense
NM_001407631.1:c.121C>G	NP_001394560.1:p.His41Asp	missense
NM_001407632.1:c.121C>G	NP_001394561.1:p.His41Asp	missense
NM_001407633.1:c.121C>G	NP_001394562.1:p.His41Asp	missense
NM_001407634.1:c.121C>G	NP_001394563.1:p.His41Asp	missense
NM_001407635.1:c.121C>G	NP_001394564.1:p.His41Asp	missense
NM_001407636.1:c.121C>G	NP_001394565.1:p.His41Asp	missense
NM_001407637.1:c.121C>G	NP_001394566.1:p.His41Asp	missense
NM_001407638.1:c.121C>G	NP_001394567.1:p.His41Asp	missense
NM_001407639.1:c.121C>G	NP_001394568.1:p.His41Asp	missense
NM_001407640.1:c.121C>G	NP_001394569.1:p.His41Asp	missense
NM_001407641.1:c.121C>G	NP_001394570.1:p.His41Asp	missense
NM_001407642.1:c.121C>G	NP_001394571.1:p.His41Asp	missense
NM_001407644.1:c.121C>G	NP_001394573.1:p.His41Asp	missense
NM_001407645.1:c.121C>G	NP_001394574.1:p.His41Asp	missense
NM_001407646.1:c.121C>G	NP_001394575.1:p.His41Asp	missense
NM_001407647.1:c.121C>G	NP_001394576.1:p.His41Asp	missense
NM_001407648.1:c.121C>G	NP_001394577.1:p.His41Asp	missense
NM_001407649.1:c.121C>G	NP_001394578.1:p.His41Asp	missense
NM_001407652.1:c.121C>G	NP_001394581.1:p.His41Asp	missense
NM_001407653.1:c.121C>G	NP_001394582.1:p.His41Asp	missense
NM_001407654.1:c.121C>G	NP_001394583.1:p.His41Asp	missense
NM_001407655.1:c.121C>G	NP_001394584.1:p.His41Asp	missense
NM_001407656.1:c.121C>G	NP_001394585.1:p.His41Asp	missense
NM_001407657.1:c.121C>G	NP_001394586.1:p.His41Asp	missense
NM_001407658.1:c.121C>G	NP_001394587.1:p.His41Asp	missense
NM_001407659.1:c.121C>G	NP_001394588.1:p.His41Asp	missense
NM_001407660.1:c.121C>G	NP_001394589.1:p.His41Asp	missense
NM_001407661.1:c.121C>G	NP_001394590.1:p.His41Asp	missense
NM_001407662.1:c.121C>G	NP_001394591.1:p.His41Asp	missense
NM_001407663.1:c.121C>G	NP_001394592.1:p.His41Asp	missense
NM_001407664.1:c.121C>G	NP_001394593.1:p.His41Asp	missense
NM_001407665.1:c.121C>G	NP_001394594.1:p.His41Asp	missense
NM_001407666.1:c.121C>G	NP_001394595.1:p.His41Asp	missense
NM_001407667.1:c.121C>G	NP_001394596.1:p.His41Asp	missense
NM_001407668.1:c.121C>G	NP_001394597.1:p.His41Asp	missense
NM_001407669.1:c.121C>G	NP_001394598.1:p.His41Asp	missense
NM_001407670.1:c.121C>G	NP_001394599.1:p.His41Asp	missense
NM_001407671.1:c.121C>G	NP_001394600.1:p.His41Asp	missense
NM_001407672.1:c.121C>G	NP_001394601.1:p.His41Asp	missense
NM_001407673.1:c.121C>G	NP_001394602.1:p.His41Asp	missense
NM_001407674.1:c.121C>G	NP_001394603.1:p.His41Asp	missense
NM_001407675.1:c.121C>G	NP_001394604.1:p.His41Asp	missense
NM_001407676.1:c.121C>G	NP_001394605.1:p.His41Asp	missense
NM_001407677.1:c.121C>G	NP_001394606.1:p.His41Asp	missense
NM_001407678.1:c.121C>G	NP_001394607.1:p.His41Asp	missense
NM_001407679.1:c.121C>G	NP_001394608.1:p.His41Asp	missense
NM_001407680.1:c.121C>G	NP_001394609.1:p.His41Asp	missense
NM_001407681.1:c.121C>G	NP_001394610.1:p.His41Asp	missense
NM_001407682.1:c.121C>G	NP_001394611.1:p.His41Asp	missense
NM_001407683.1:c.121C>G	NP_001394612.1:p.His41Asp	missense
NM_001407684.1:c.121C>G	NP_001394613.1:p.His41Asp	missense
NM_001407685.1:c.121C>G	NP_001394614.1:p.His41Asp	missense
NM_001407686.1:c.121C>G	NP_001394615.1:p.His41Asp	missense
NM_001407687.1:c.121C>G	NP_001394616.1:p.His41Asp	missense
NM_001407688.1:c.121C>G	NP_001394617.1:p.His41Asp	missense
NM_001407689.1:c.121C>G	NP_001394618.1:p.His41Asp	missense
NM_001407690.1:c.121C>G	NP_001394619.1:p.His41Asp	missense
NM_001407691.1:c.121C>G	NP_001394620.1:p.His41Asp	missense
NM_001407694.1:c.-137C>G
NM_001407695.1:c.-141C>G
NM_001407696.1:c.-137C>G
NM_001407697.1:c.-21C>G
NM_001407724.1:c.-137C>G
NM_001407725.1:c.-21C>G
NM_001407727.1:c.-137C>G
NM_001407728.1:c.-21C>G
NM_001407729.1:c.-21C>G
NM_001407730.1:c.-21C>G
NM_001407731.1:c.-137C>G
NM_001407733.1:c.-137C>G
NM_001407734.1:c.-21C>G
NM_001407735.1:c.-21C>G
NM_001407737.1:c.-21C>G
NM_001407739.1:c.-21C>G
NM_001407740.1:c.-21C>G
NM_001407741.1:c.-21C>G
NM_001407743.1:c.-21C>G
NM_001407745.1:c.-21C>G
NM_001407746.1:c.-137C>G
NM_001407748.1:c.-21C>G
NM_001407749.1:c.-137C>G
NM_001407752.1:c.-21C>G
NM_001407838.1:c.-21C>G
NM_001407839.1:c.-21C>G
NM_001407841.1:c.-17C>G
NM_001407842.1:c.-137C>G
NM_001407843.1:c.-137C>G
NM_001407844.1:c.-21C>G
NM_001407846.1:c.-21C>G
NM_001407847.1:c.-21C>G
NM_001407848.1:c.-21C>G
NM_001407850.1:c.-21C>G
NM_001407851.1:c.-21C>G
NM_001407853.1:c.-68C>G
NM_001407854.1:c.121C>G	NP_001394783.1:p.His41Asp	missense
NM_001407858.1:c.121C>G	NP_001394787.1:p.His41Asp	missense
NM_001407859.1:c.121C>G	NP_001394788.1:p.His41Asp	missense
NM_001407860.1:c.121C>G	NP_001394789.1:p.His41Asp	missense
NM_001407861.1:c.121C>G	NP_001394790.1:p.His41Asp	missense
NM_001407862.1:c.121C>G	NP_001394791.1:p.His41Asp	missense
NM_001407863.1:c.121C>G	NP_001394792.1:p.His41Asp	missense
NM_001407874.1:c.121C>G	NP_001394803.1:p.His41Asp	missense
NM_001407875.1:c.121C>G	NP_001394804.1:p.His41Asp	missense
NM_001407879.1:c.-68C>G
NM_001407882.1:c.-68C>G
NM_001407884.1:c.-68C>G
NM_001407885.1:c.-68C>G
NM_001407886.1:c.-68C>G
NM_001407887.1:c.-68C>G
NM_001407889.1:c.-184C>G
NM_001407894.1:c.-68C>G
NM_001407895.1:c.-68C>G
NM_001407896.1:c.-68C>G
NM_001407897.1:c.-68C>G
NM_001407899.1:c.-68C>G
NM_001407900.1:c.-184C>G
NM_001407904.1:c.-68C>G
NM_001407906.1:c.-68C>G
NM_001407907.1:c.-68C>G
NM_001407908.1:c.-68C>G
NM_001407909.1:c.-68C>G
NM_001407910.1:c.-68C>G
NM_001407915.1:c.-68C>G
NM_001407916.1:c.-68C>G
NM_001407917.1:c.-68C>G
NM_001407918.1:c.-68C>G
NM_001407919.1:c.121C>G	NP_001394848.1:p.His41Asp	missense
NM_001407920.1:c.-21C>G
NM_001407921.1:c.-21C>G
NM_001407922.1:c.-21C>G
NM_001407923.1:c.-21C>G
NM_001407926.1:c.-21C>G
NM_001407927.1:c.-21C>G
NM_001407930.1:c.-137C>G
NM_001407933.1:c.-21C>G
NM_001407934.1:c.-21C>G
NM_001407935.1:c.-21C>G
NM_001407937.1:c.121C>G	NP_001394866.1:p.His41Asp	missense
NM_001407938.1:c.121C>G	NP_001394867.1:p.His41Asp	missense
NM_001407939.1:c.121C>G	NP_001394868.1:p.His41Asp	missense
NM_001407940.1:c.121C>G	NP_001394869.1:p.His41Asp	missense
NM_001407941.1:c.121C>G	NP_001394870.1:p.His41Asp	missense
NM_001407942.1:c.-137C>G
NM_001407943.1:c.-21C>G
NM_001407944.1:c.-21C>G
NM_001407946.1:c.-68C>G
NM_001407947.1:c.-68C>G
NM_001407948.1:c.-68C>G
NM_001407949.1:c.-68C>G
NM_001407950.1:c.-68C>G
NM_001407951.1:c.-68C>G
NM_001407952.1:c.-68C>G
NM_001407953.1:c.-68C>G
NM_001407954.1:c.-68C>G
NM_001407955.1:c.-68C>G
NM_001407956.1:c.-68C>G
NM_001407957.1:c.-68C>G
NM_001407958.1:c.-68C>G
NM_001407960.1:c.-183C>G
NM_001407962.1:c.-183C>G
NM_001407964.1:c.-21C>G
NM_001407965.1:c.-299C>G
NM_001407968.1:c.121C>G	NP_001394897.1:p.His41Asp	missense
NM_001407969.1:c.121C>G	NP_001394898.1:p.His41Asp	missense
NM_001407970.1:c.121C>G	NP_001394899.1:p.His41Asp	missense
NM_001407971.1:c.121C>G	NP_001394900.1:p.His41Asp	missense
NM_001407972.1:c.121C>G	NP_001394901.1:p.His41Asp	missense
NM_001407973.1:c.121C>G	NP_001394902.1:p.His41Asp	missense
NM_001407974.1:c.121C>G	NP_001394903.1:p.His41Asp	missense
NM_001407975.1:c.121C>G	NP_001394904.1:p.His41Asp	missense
NM_001407976.1:c.121C>G	NP_001394905.1:p.His41Asp	missense
NM_001407977.1:c.121C>G	NP_001394906.1:p.His41Asp	missense
NM_001407978.1:c.121C>G	NP_001394907.1:p.His41Asp	missense
NM_001407979.1:c.121C>G	NP_001394908.1:p.His41Asp	missense
NM_001407980.1:c.121C>G	NP_001394909.1:p.His41Asp	missense
NM_001407981.1:c.121C>G	NP_001394910.1:p.His41Asp	missense
NM_001407982.1:c.121C>G	NP_001394911.1:p.His41Asp	missense
NM_001407983.1:c.121C>G	NP_001394912.1:p.His41Asp	missense
NM_001407984.1:c.121C>G	NP_001394913.1:p.His41Asp	missense
NM_001407985.1:c.121C>G	NP_001394914.1:p.His41Asp	missense
NM_001407986.1:c.121C>G	NP_001394915.1:p.His41Asp	missense
NM_001407990.1:c.121C>G	NP_001394919.1:p.His41Asp	missense
NM_001407991.1:c.121C>G	NP_001394920.1:p.His41Asp	missense
NM_001407992.1:c.121C>G	NP_001394921.1:p.His41Asp	missense
NM_001407993.1:c.121C>G	NP_001394922.1:p.His41Asp	missense
NM_001408392.1:c.121C>G	NP_001395321.1:p.His41Asp	missense
NM_001408396.1:c.121C>G	NP_001395325.1:p.His41Asp	missense
NM_001408397.1:c.121C>G	NP_001395326.1:p.His41Asp	missense
NM_001408398.1:c.121C>G	NP_001395327.1:p.His41Asp	missense
NM_001408399.1:c.121C>G	NP_001395328.1:p.His41Asp	missense
NM_001408400.1:c.121C>G	NP_001395329.1:p.His41Asp	missense
NM_001408401.1:c.121C>G	NP_001395330.1:p.His41Asp	missense
NM_001408402.1:c.121C>G	NP_001395331.1:p.His41Asp	missense
NM_001408403.1:c.121C>G	NP_001395332.1:p.His41Asp	missense
NM_001408404.1:c.121C>G	NP_001395333.1:p.His41Asp	missense
NM_001408406.1:c.121C>G	NP_001395335.1:p.His41Asp	missense
NM_001408407.1:c.121C>G	NP_001395336.1:p.His41Asp	missense
NM_001408408.1:c.121C>G	NP_001395337.1:p.His41Asp	missense
NM_001408409.1:c.121C>G	NP_001395338.1:p.His41Asp	missense
NM_001408410.1:c.-21C>G
NM_001408411.1:c.121C>G	NP_001395340.1:p.His41Asp	missense
NM_001408412.1:c.121C>G	NP_001395341.1:p.His41Asp	missense
NM_001408413.1:c.121C>G	NP_001395342.1:p.His41Asp	missense
NM_001408414.1:c.121C>G	NP_001395343.1:p.His41Asp	missense
NM_001408415.1:c.121C>G	NP_001395344.1:p.His41Asp	missense
NM_001408416.1:c.121C>G	NP_001395345.1:p.His41Asp	missense
NM_001408418.1:c.121C>G	NP_001395347.1:p.His41Asp	missense
NM_001408419.1:c.121C>G	NP_001395348.1:p.His41Asp	missense
NM_001408420.1:c.121C>G	NP_001395349.1:p.His41Asp	missense
NM_001408421.1:c.121C>G	NP_001395350.1:p.His41Asp	missense
NM_001408422.1:c.121C>G	NP_001395351.1:p.His41Asp	missense
NM_001408423.1:c.121C>G	NP_001395352.1:p.His41Asp	missense
NM_001408424.1:c.121C>G	NP_001395353.1:p.His41Asp	missense
NM_001408425.1:c.121C>G	NP_001395354.1:p.His41Asp	missense
NM_001408426.1:c.121C>G	NP_001395355.1:p.His41Asp	missense
NM_001408427.1:c.121C>G	NP_001395356.1:p.His41Asp	missense
NM_001408428.1:c.121C>G	NP_001395357.1:p.His41Asp	missense
NM_001408429.1:c.121C>G	NP_001395358.1:p.His41Asp	missense
NM_001408430.1:c.121C>G	NP_001395359.1:p.His41Asp	missense
NM_001408431.1:c.121C>G	NP_001395360.1:p.His41Asp	missense
NM_001408432.1:c.121C>G	NP_001395361.1:p.His41Asp	missense
NM_001408433.1:c.121C>G	NP_001395362.1:p.His41Asp	missense
NM_001408434.1:c.121C>G	NP_001395363.1:p.His41Asp	missense
NM_001408435.1:c.121C>G	NP_001395364.1:p.His41Asp	missense
NM_001408436.1:c.121C>G	NP_001395365.1:p.His41Asp	missense
NM_001408437.1:c.121C>G	NP_001395366.1:p.His41Asp	missense
NM_001408438.1:c.121C>G	NP_001395367.1:p.His41Asp	missense
NM_001408439.1:c.121C>G	NP_001395368.1:p.His41Asp	missense
NM_001408440.1:c.121C>G	NP_001395369.1:p.His41Asp	missense
NM_001408441.1:c.121C>G	NP_001395370.1:p.His41Asp	missense
NM_001408442.1:c.121C>G	NP_001395371.1:p.His41Asp	missense
NM_001408443.1:c.121C>G	NP_001395372.1:p.His41Asp	missense
NM_001408444.1:c.121C>G	NP_001395373.1:p.His41Asp	missense
NM_001408445.1:c.121C>G	NP_001395374.1:p.His41Asp	missense
NM_001408446.1:c.121C>G	NP_001395375.1:p.His41Asp	missense
NM_001408447.1:c.121C>G	NP_001395376.1:p.His41Asp	missense
NM_001408448.1:c.121C>G	NP_001395377.1:p.His41Asp	missense
NM_001408450.1:c.121C>G	NP_001395379.1:p.His41Asp	missense
NM_001408452.1:c.-21C>G
NM_001408453.1:c.-21C>G
NM_001408455.1:c.-137C>G
NM_001408456.1:c.-137C>G
NM_001408458.1:c.-21C>G
NM_001408462.1:c.-21C>G
NM_001408463.1:c.-21C>G
NM_001408465.1:c.-141C>G
NM_001408466.1:c.-21C>G
NM_001408468.1:c.-137C>G
NM_001408469.1:c.-21C>G
NM_001408470.1:c.-21C>G
NM_001408472.1:c.121C>G	NP_001395401.1:p.His41Asp	missense
NM_001408473.1:c.121C>G	NP_001395402.1:p.His41Asp	missense
NM_001408474.1:c.121C>G	NP_001395403.1:p.His41Asp	missense
NM_001408475.1:c.121C>G	NP_001395404.1:p.His41Asp	missense
NM_001408476.1:c.121C>G	NP_001395405.1:p.His41Asp	missense
NM_001408478.1:c.-68C>G
NM_001408479.1:c.-68C>G
NM_001408480.1:c.-68C>G
NM_001408481.1:c.-68C>G
NM_001408482.1:c.-68C>G
NM_001408483.1:c.-68C>G
NM_001408484.1:c.-68C>G
NM_001408485.1:c.-68C>G
NM_001408489.1:c.-68C>G
NM_001408490.1:c.-68C>G
NM_001408491.1:c.-68C>G
NM_001408492.1:c.-184C>G
NM_001408493.1:c.-68C>G
NM_001408494.1:c.121C>G	NP_001395423.1:p.His41Asp	missense
NM_001408495.1:c.121C>G	NP_001395424.1:p.His41Asp	missense
NM_001408497.1:c.-21C>G
NM_001408499.1:c.-21C>G
NM_001408500.1:c.-21C>G
NM_001408501.1:c.-137C>G
NM_001408502.1:c.-68C>G
NM_001408503.1:c.-21C>G
NM_001408504.1:c.-21C>G
NM_001408505.1:c.-21C>G
NM_001408506.1:c.-68C>G
NM_001408507.1:c.-68C>G
NM_001408508.1:c.-68C>G
NM_001408509.1:c.-68C>G
NM_001408510.1:c.-183C>G
NM_001408512.1:c.-183C>G
NM_001408513.1:c.-68C>G
NM_001408514.1:c.-68C>G
NM_007297.4:c.-8+8278C>G		intron variant
NM_007298.4:c.121C>G	NP_009229.2:p.His41Asp	missense
NM_007299.4:c.121C>G	NP_009230.2:p.His41Asp	missense
NM_007300.4:c.121C>G	NP_009231.2:p.His41Asp	missense
NM_007304.2:c.121C>G	NP_009235.2:p.His41Asp	missense
NR_027676.2:n.323C>G		non-coding transcript variant
NC_000017.11:g.43115739G>C
NC_000017.10:g.41267756G>C
NG_005905.2:g.102245C>G
LRG_292:g.102245C>G
LRG_292t1:c.121C>G	LRG_292p1:p.His41Asp

... more HGVS ... less HGVS

Protein change

H41D

Other names

Canonical SPDI

NC_000017.11:43115738:G:C

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

functionally_abnormal; Sequence Ontology [ SO:0002218]

The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.121C>G, a MISSENSE variant, produced a function score of -2.14, corresponding to a functional classification of LOSS_OF_FUNCTION. 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.

Links

dbSNP: rs1060502353 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	not provided (1)	no classification provided	-	RCV001077000.3
Hereditary breast ovarian cancer syndrome	Likely pathogenic (1)	criteria provided, single submitter	Dec 29, 2022	RCV003645178.2

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 pathogenic (Dec 29, 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: SCV004429688.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (7) PubMed: 15168169‚ 16403807‚ 20103620‚ 21725363‚ 23161852‚ 24489791‚ 30209399 Comment: This variant disrupts the p.His41 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15168169, 16403807, … (more) This variant disrupts the p.His41 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15168169, 16403807, 20103620, 21725363, 23161852, 24489791, 30209399; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 868161). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 41 of the BRCA1 protein (p.His41Asp). (less)
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: SCV001242857.1 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: LOSS_OF_FUNCTION:-2.14174273520893

Comment:

This variant disrupts the p.His41 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15168169, 16403807, 20103620, 21725363, 23161852, 24489791, 30209399; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function. ClinVar contains an entry for this variant (Variation ID: 868161). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 41 of the BRCA1 protein (p.His41Asp).

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_abnormal (SO:0002218)	saturation genome editing in haploid cells Method citation(s): PubMed(1)	LOSS_OF_FUNCTION:-2.14174273520893	Brotman Baty Institute, University of Washington Accession: SCV001242857.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.121C>G, a MISSENSE variant, produced a function score of -2.14, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.121C>G, a MISSENSE variant, produced a function score of -2.14, corresponding to a functional classification of LOSS_OF_FUNCTION. 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
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Multifactorial likelihood assessment of BRCA1 and BRCA2 missense variants confirms that BRCA1:c.122A>G(p.His41Arg) is a pathogenic mutation.	Whiley PJ	PloS one	2014	PMID: 24489791
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
Identification and evaluation of 55 genetic variations in the BRCA1 and the BRCA2 genes of patients from 50 Japanese breast cancer families.	Kawahara M	Journal of human genetics	2004	PMID: 15168169
https://sge.gs.washington.edu/BRCA1/	-	-	-	-

Text-mined citations for rs1060502353 ...

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 Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.121C>G (p.His41Asp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1060502353 ...