VCV000037393.20 - ClinVar

NM_007294.4(BRCA1):c.116G>T (p.Cys39Phe)

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.

(8)

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.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.116G>T (p.Cys39Phe)

Variation ID: 37393 Accession: VCV000037393.20

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43115744 (GRCh38) [ NCBI UCSC ] 17: 41267761 (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	Sep 27, 2014	May 1, 2024	Nov 22, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.116G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.Cys39Phe	missense
NM_001407571.1:c.-73G>T
NM_001407581.1:c.116G>T	NP_001394510.1:p.Cys39Phe	missense
NM_001407582.1:c.116G>T	NP_001394511.1:p.Cys39Phe	missense
NM_001407583.1:c.116G>T	NP_001394512.1:p.Cys39Phe	missense
NM_001407585.1:c.116G>T	NP_001394514.1:p.Cys39Phe	missense
NM_001407587.1:c.116G>T	NP_001394516.1:p.Cys39Phe	missense
NM_001407590.1:c.116G>T	NP_001394519.1:p.Cys39Phe	missense
NM_001407591.1:c.116G>T	NP_001394520.1:p.Cys39Phe	missense
NM_001407593.1:c.116G>T	NP_001394522.1:p.Cys39Phe	missense
NM_001407594.1:c.116G>T	NP_001394523.1:p.Cys39Phe	missense
NM_001407596.1:c.116G>T	NP_001394525.1:p.Cys39Phe	missense
NM_001407597.1:c.116G>T	NP_001394526.1:p.Cys39Phe	missense
NM_001407598.1:c.116G>T	NP_001394527.1:p.Cys39Phe	missense
NM_001407602.1:c.116G>T	NP_001394531.1:p.Cys39Phe	missense
NM_001407603.1:c.116G>T	NP_001394532.1:p.Cys39Phe	missense
NM_001407605.1:c.116G>T	NP_001394534.1:p.Cys39Phe	missense
NM_001407610.1:c.116G>T	NP_001394539.1:p.Cys39Phe	missense
NM_001407611.1:c.116G>T	NP_001394540.1:p.Cys39Phe	missense
NM_001407612.1:c.116G>T	NP_001394541.1:p.Cys39Phe	missense
NM_001407613.1:c.116G>T	NP_001394542.1:p.Cys39Phe	missense
NM_001407614.1:c.116G>T	NP_001394543.1:p.Cys39Phe	missense
NM_001407615.1:c.116G>T	NP_001394544.1:p.Cys39Phe	missense
NM_001407616.1:c.116G>T	NP_001394545.1:p.Cys39Phe	missense
NM_001407617.1:c.116G>T	NP_001394546.1:p.Cys39Phe	missense
NM_001407618.1:c.116G>T	NP_001394547.1:p.Cys39Phe	missense
NM_001407619.1:c.116G>T	NP_001394548.1:p.Cys39Phe	missense
NM_001407620.1:c.116G>T	NP_001394549.1:p.Cys39Phe	missense
NM_001407621.1:c.116G>T	NP_001394550.1:p.Cys39Phe	missense
NM_001407622.1:c.116G>T	NP_001394551.1:p.Cys39Phe	missense
NM_001407623.1:c.116G>T	NP_001394552.1:p.Cys39Phe	missense
NM_001407624.1:c.116G>T	NP_001394553.1:p.Cys39Phe	missense
NM_001407625.1:c.116G>T	NP_001394554.1:p.Cys39Phe	missense
NM_001407626.1:c.116G>T	NP_001394555.1:p.Cys39Phe	missense
NM_001407627.1:c.116G>T	NP_001394556.1:p.Cys39Phe	missense
NM_001407628.1:c.116G>T	NP_001394557.1:p.Cys39Phe	missense
NM_001407629.1:c.116G>T	NP_001394558.1:p.Cys39Phe	missense
NM_001407630.1:c.116G>T	NP_001394559.1:p.Cys39Phe	missense
NM_001407631.1:c.116G>T	NP_001394560.1:p.Cys39Phe	missense
NM_001407632.1:c.116G>T	NP_001394561.1:p.Cys39Phe	missense
NM_001407633.1:c.116G>T	NP_001394562.1:p.Cys39Phe	missense
NM_001407634.1:c.116G>T	NP_001394563.1:p.Cys39Phe	missense
NM_001407635.1:c.116G>T	NP_001394564.1:p.Cys39Phe	missense
NM_001407636.1:c.116G>T	NP_001394565.1:p.Cys39Phe	missense
NM_001407637.1:c.116G>T	NP_001394566.1:p.Cys39Phe	missense
NM_001407638.1:c.116G>T	NP_001394567.1:p.Cys39Phe	missense
NM_001407639.1:c.116G>T	NP_001394568.1:p.Cys39Phe	missense
NM_001407640.1:c.116G>T	NP_001394569.1:p.Cys39Phe	missense
NM_001407641.1:c.116G>T	NP_001394570.1:p.Cys39Phe	missense
NM_001407642.1:c.116G>T	NP_001394571.1:p.Cys39Phe	missense
NM_001407644.1:c.116G>T	NP_001394573.1:p.Cys39Phe	missense
NM_001407645.1:c.116G>T	NP_001394574.1:p.Cys39Phe	missense
NM_001407646.1:c.116G>T	NP_001394575.1:p.Cys39Phe	missense
NM_001407647.1:c.116G>T	NP_001394576.1:p.Cys39Phe	missense
NM_001407648.1:c.116G>T	NP_001394577.1:p.Cys39Phe	missense
NM_001407649.1:c.116G>T	NP_001394578.1:p.Cys39Phe	missense
NM_001407652.1:c.116G>T	NP_001394581.1:p.Cys39Phe	missense
NM_001407653.1:c.116G>T	NP_001394582.1:p.Cys39Phe	missense
NM_001407654.1:c.116G>T	NP_001394583.1:p.Cys39Phe	missense
NM_001407655.1:c.116G>T	NP_001394584.1:p.Cys39Phe	missense
NM_001407656.1:c.116G>T	NP_001394585.1:p.Cys39Phe	missense
NM_001407657.1:c.116G>T	NP_001394586.1:p.Cys39Phe	missense
NM_001407658.1:c.116G>T	NP_001394587.1:p.Cys39Phe	missense
NM_001407659.1:c.116G>T	NP_001394588.1:p.Cys39Phe	missense
NM_001407660.1:c.116G>T	NP_001394589.1:p.Cys39Phe	missense
NM_001407661.1:c.116G>T	NP_001394590.1:p.Cys39Phe	missense
NM_001407662.1:c.116G>T	NP_001394591.1:p.Cys39Phe	missense
NM_001407663.1:c.116G>T	NP_001394592.1:p.Cys39Phe	missense
NM_001407664.1:c.116G>T	NP_001394593.1:p.Cys39Phe	missense
NM_001407665.1:c.116G>T	NP_001394594.1:p.Cys39Phe	missense
NM_001407666.1:c.116G>T	NP_001394595.1:p.Cys39Phe	missense
NM_001407667.1:c.116G>T	NP_001394596.1:p.Cys39Phe	missense
NM_001407668.1:c.116G>T	NP_001394597.1:p.Cys39Phe	missense
NM_001407669.1:c.116G>T	NP_001394598.1:p.Cys39Phe	missense
NM_001407670.1:c.116G>T	NP_001394599.1:p.Cys39Phe	missense
NM_001407671.1:c.116G>T	NP_001394600.1:p.Cys39Phe	missense
NM_001407672.1:c.116G>T	NP_001394601.1:p.Cys39Phe	missense
NM_001407673.1:c.116G>T	NP_001394602.1:p.Cys39Phe	missense
NM_001407674.1:c.116G>T	NP_001394603.1:p.Cys39Phe	missense
NM_001407675.1:c.116G>T	NP_001394604.1:p.Cys39Phe	missense
NM_001407676.1:c.116G>T	NP_001394605.1:p.Cys39Phe	missense
NM_001407677.1:c.116G>T	NP_001394606.1:p.Cys39Phe	missense
NM_001407678.1:c.116G>T	NP_001394607.1:p.Cys39Phe	missense
NM_001407679.1:c.116G>T	NP_001394608.1:p.Cys39Phe	missense
NM_001407680.1:c.116G>T	NP_001394609.1:p.Cys39Phe	missense
NM_001407681.1:c.116G>T	NP_001394610.1:p.Cys39Phe	missense
NM_001407682.1:c.116G>T	NP_001394611.1:p.Cys39Phe	missense
NM_001407683.1:c.116G>T	NP_001394612.1:p.Cys39Phe	missense
NM_001407684.1:c.116G>T	NP_001394613.1:p.Cys39Phe	missense
NM_001407685.1:c.116G>T	NP_001394614.1:p.Cys39Phe	missense
NM_001407686.1:c.116G>T	NP_001394615.1:p.Cys39Phe	missense
NM_001407687.1:c.116G>T	NP_001394616.1:p.Cys39Phe	missense
NM_001407688.1:c.116G>T	NP_001394617.1:p.Cys39Phe	missense
NM_001407689.1:c.116G>T	NP_001394618.1:p.Cys39Phe	missense
NM_001407690.1:c.116G>T	NP_001394619.1:p.Cys39Phe	missense
NM_001407691.1:c.116G>T	NP_001394620.1:p.Cys39Phe	missense
NM_001407694.1:c.-142G>T
NM_001407695.1:c.-146G>T
NM_001407696.1:c.-142G>T
NM_001407697.1:c.-26G>T
NM_001407724.1:c.-142G>T
NM_001407725.1:c.-26G>T
NM_001407727.1:c.-142G>T
NM_001407728.1:c.-26G>T
NM_001407729.1:c.-26G>T
NM_001407730.1:c.-26G>T
NM_001407731.1:c.-142G>T
NM_001407733.1:c.-142G>T
NM_001407734.1:c.-26G>T
NM_001407735.1:c.-26G>T
NM_001407737.1:c.-26G>T
NM_001407739.1:c.-26G>T
NM_001407740.1:c.-26G>T
NM_001407741.1:c.-26G>T
NM_001407743.1:c.-26G>T
NM_001407745.1:c.-26G>T
NM_001407746.1:c.-142G>T
NM_001407748.1:c.-26G>T
NM_001407749.1:c.-142G>T
NM_001407752.1:c.-26G>T
NM_001407838.1:c.-26G>T
NM_001407839.1:c.-26G>T
NM_001407841.1:c.-22G>T
NM_001407842.1:c.-142G>T
NM_001407843.1:c.-142G>T
NM_001407844.1:c.-26G>T
NM_001407846.1:c.-26G>T
NM_001407847.1:c.-26G>T
NM_001407848.1:c.-26G>T
NM_001407850.1:c.-26G>T
NM_001407851.1:c.-26G>T
NM_001407853.1:c.-73G>T
NM_001407854.1:c.116G>T	NP_001394783.1:p.Cys39Phe	missense
NM_001407858.1:c.116G>T	NP_001394787.1:p.Cys39Phe	missense
NM_001407859.1:c.116G>T	NP_001394788.1:p.Cys39Phe	missense
NM_001407860.1:c.116G>T	NP_001394789.1:p.Cys39Phe	missense
NM_001407861.1:c.116G>T	NP_001394790.1:p.Cys39Phe	missense
NM_001407862.1:c.116G>T	NP_001394791.1:p.Cys39Phe	missense
NM_001407863.1:c.116G>T	NP_001394792.1:p.Cys39Phe	missense
NM_001407874.1:c.116G>T	NP_001394803.1:p.Cys39Phe	missense
NM_001407875.1:c.116G>T	NP_001394804.1:p.Cys39Phe	missense
NM_001407879.1:c.-73G>T
NM_001407882.1:c.-73G>T
NM_001407884.1:c.-73G>T
NM_001407885.1:c.-73G>T
NM_001407886.1:c.-73G>T
NM_001407887.1:c.-73G>T
NM_001407889.1:c.-189G>T
NM_001407894.1:c.-73G>T
NM_001407895.1:c.-73G>T
NM_001407896.1:c.-73G>T
NM_001407897.1:c.-73G>T
NM_001407899.1:c.-73G>T
NM_001407900.1:c.-189G>T
NM_001407904.1:c.-73G>T
NM_001407906.1:c.-73G>T
NM_001407907.1:c.-73G>T
NM_001407908.1:c.-73G>T
NM_001407909.1:c.-73G>T
NM_001407910.1:c.-73G>T
NM_001407915.1:c.-73G>T
NM_001407916.1:c.-73G>T
NM_001407917.1:c.-73G>T
NM_001407918.1:c.-73G>T
NM_001407919.1:c.116G>T	NP_001394848.1:p.Cys39Phe	missense
NM_001407920.1:c.-26G>T
NM_001407921.1:c.-26G>T
NM_001407922.1:c.-26G>T
NM_001407923.1:c.-26G>T
NM_001407926.1:c.-26G>T
NM_001407927.1:c.-26G>T
NM_001407930.1:c.-142G>T
NM_001407933.1:c.-26G>T
NM_001407934.1:c.-26G>T
NM_001407935.1:c.-26G>T
NM_001407937.1:c.116G>T	NP_001394866.1:p.Cys39Phe	missense
NM_001407938.1:c.116G>T	NP_001394867.1:p.Cys39Phe	missense
NM_001407939.1:c.116G>T	NP_001394868.1:p.Cys39Phe	missense
NM_001407940.1:c.116G>T	NP_001394869.1:p.Cys39Phe	missense
NM_001407941.1:c.116G>T	NP_001394870.1:p.Cys39Phe	missense
NM_001407942.1:c.-142G>T
NM_001407943.1:c.-26G>T
NM_001407944.1:c.-26G>T
NM_001407946.1:c.-73G>T
NM_001407947.1:c.-73G>T
NM_001407948.1:c.-73G>T
NM_001407949.1:c.-73G>T
NM_001407950.1:c.-73G>T
NM_001407951.1:c.-73G>T
NM_001407952.1:c.-73G>T
NM_001407953.1:c.-73G>T
NM_001407954.1:c.-73G>T
NM_001407955.1:c.-73G>T
NM_001407956.1:c.-73G>T
NM_001407957.1:c.-73G>T
NM_001407958.1:c.-73G>T
NM_001407960.1:c.-188G>T
NM_001407962.1:c.-188G>T
NM_001407964.1:c.-26G>T
NM_001407965.1:c.-304G>T
NM_001407968.1:c.116G>T	NP_001394897.1:p.Cys39Phe	missense
NM_001407969.1:c.116G>T	NP_001394898.1:p.Cys39Phe	missense
NM_001407970.1:c.116G>T	NP_001394899.1:p.Cys39Phe	missense
NM_001407971.1:c.116G>T	NP_001394900.1:p.Cys39Phe	missense
NM_001407972.1:c.116G>T	NP_001394901.1:p.Cys39Phe	missense
NM_001407973.1:c.116G>T	NP_001394902.1:p.Cys39Phe	missense
NM_001407974.1:c.116G>T	NP_001394903.1:p.Cys39Phe	missense
NM_001407975.1:c.116G>T	NP_001394904.1:p.Cys39Phe	missense
NM_001407976.1:c.116G>T	NP_001394905.1:p.Cys39Phe	missense
NM_001407977.1:c.116G>T	NP_001394906.1:p.Cys39Phe	missense
NM_001407978.1:c.116G>T	NP_001394907.1:p.Cys39Phe	missense
NM_001407979.1:c.116G>T	NP_001394908.1:p.Cys39Phe	missense
NM_001407980.1:c.116G>T	NP_001394909.1:p.Cys39Phe	missense
NM_001407981.1:c.116G>T	NP_001394910.1:p.Cys39Phe	missense
NM_001407982.1:c.116G>T	NP_001394911.1:p.Cys39Phe	missense
NM_001407983.1:c.116G>T	NP_001394912.1:p.Cys39Phe	missense
NM_001407984.1:c.116G>T	NP_001394913.1:p.Cys39Phe	missense
NM_001407985.1:c.116G>T	NP_001394914.1:p.Cys39Phe	missense
NM_001407986.1:c.116G>T	NP_001394915.1:p.Cys39Phe	missense
NM_001407990.1:c.116G>T	NP_001394919.1:p.Cys39Phe	missense
NM_001407991.1:c.116G>T	NP_001394920.1:p.Cys39Phe	missense
NM_001407992.1:c.116G>T	NP_001394921.1:p.Cys39Phe	missense
NM_001407993.1:c.116G>T	NP_001394922.1:p.Cys39Phe	missense
NM_001408392.1:c.116G>T	NP_001395321.1:p.Cys39Phe	missense
NM_001408396.1:c.116G>T	NP_001395325.1:p.Cys39Phe	missense
NM_001408397.1:c.116G>T	NP_001395326.1:p.Cys39Phe	missense
NM_001408398.1:c.116G>T	NP_001395327.1:p.Cys39Phe	missense
NM_001408399.1:c.116G>T	NP_001395328.1:p.Cys39Phe	missense
NM_001408400.1:c.116G>T	NP_001395329.1:p.Cys39Phe	missense
NM_001408401.1:c.116G>T	NP_001395330.1:p.Cys39Phe	missense
NM_001408402.1:c.116G>T	NP_001395331.1:p.Cys39Phe	missense
NM_001408403.1:c.116G>T	NP_001395332.1:p.Cys39Phe	missense
NM_001408404.1:c.116G>T	NP_001395333.1:p.Cys39Phe	missense
NM_001408406.1:c.116G>T	NP_001395335.1:p.Cys39Phe	missense
NM_001408407.1:c.116G>T	NP_001395336.1:p.Cys39Phe	missense
NM_001408408.1:c.116G>T	NP_001395337.1:p.Cys39Phe	missense
NM_001408409.1:c.116G>T	NP_001395338.1:p.Cys39Phe	missense
NM_001408410.1:c.-26G>T
NM_001408411.1:c.116G>T	NP_001395340.1:p.Cys39Phe	missense
NM_001408412.1:c.116G>T	NP_001395341.1:p.Cys39Phe	missense
NM_001408413.1:c.116G>T	NP_001395342.1:p.Cys39Phe	missense
NM_001408414.1:c.116G>T	NP_001395343.1:p.Cys39Phe	missense
NM_001408415.1:c.116G>T	NP_001395344.1:p.Cys39Phe	missense
NM_001408416.1:c.116G>T	NP_001395345.1:p.Cys39Phe	missense
NM_001408418.1:c.116G>T	NP_001395347.1:p.Cys39Phe	missense
NM_001408419.1:c.116G>T	NP_001395348.1:p.Cys39Phe	missense
NM_001408420.1:c.116G>T	NP_001395349.1:p.Cys39Phe	missense
NM_001408421.1:c.116G>T	NP_001395350.1:p.Cys39Phe	missense
NM_001408422.1:c.116G>T	NP_001395351.1:p.Cys39Phe	missense
NM_001408423.1:c.116G>T	NP_001395352.1:p.Cys39Phe	missense
NM_001408424.1:c.116G>T	NP_001395353.1:p.Cys39Phe	missense
NM_001408425.1:c.116G>T	NP_001395354.1:p.Cys39Phe	missense
NM_001408426.1:c.116G>T	NP_001395355.1:p.Cys39Phe	missense
NM_001408427.1:c.116G>T	NP_001395356.1:p.Cys39Phe	missense
NM_001408428.1:c.116G>T	NP_001395357.1:p.Cys39Phe	missense
NM_001408429.1:c.116G>T	NP_001395358.1:p.Cys39Phe	missense
NM_001408430.1:c.116G>T	NP_001395359.1:p.Cys39Phe	missense
NM_001408431.1:c.116G>T	NP_001395360.1:p.Cys39Phe	missense
NM_001408432.1:c.116G>T	NP_001395361.1:p.Cys39Phe	missense
NM_001408433.1:c.116G>T	NP_001395362.1:p.Cys39Phe	missense
NM_001408434.1:c.116G>T	NP_001395363.1:p.Cys39Phe	missense
NM_001408435.1:c.116G>T	NP_001395364.1:p.Cys39Phe	missense
NM_001408436.1:c.116G>T	NP_001395365.1:p.Cys39Phe	missense
NM_001408437.1:c.116G>T	NP_001395366.1:p.Cys39Phe	missense
NM_001408438.1:c.116G>T	NP_001395367.1:p.Cys39Phe	missense
NM_001408439.1:c.116G>T	NP_001395368.1:p.Cys39Phe	missense
NM_001408440.1:c.116G>T	NP_001395369.1:p.Cys39Phe	missense
NM_001408441.1:c.116G>T	NP_001395370.1:p.Cys39Phe	missense
NM_001408442.1:c.116G>T	NP_001395371.1:p.Cys39Phe	missense
NM_001408443.1:c.116G>T	NP_001395372.1:p.Cys39Phe	missense
NM_001408444.1:c.116G>T	NP_001395373.1:p.Cys39Phe	missense
NM_001408445.1:c.116G>T	NP_001395374.1:p.Cys39Phe	missense
NM_001408446.1:c.116G>T	NP_001395375.1:p.Cys39Phe	missense
NM_001408447.1:c.116G>T	NP_001395376.1:p.Cys39Phe	missense
NM_001408448.1:c.116G>T	NP_001395377.1:p.Cys39Phe	missense
NM_001408450.1:c.116G>T	NP_001395379.1:p.Cys39Phe	missense
NM_001408452.1:c.-26G>T
NM_001408453.1:c.-26G>T
NM_001408455.1:c.-142G>T
NM_001408456.1:c.-142G>T
NM_001408458.1:c.-26G>T
NM_001408462.1:c.-26G>T
NM_001408463.1:c.-26G>T
NM_001408465.1:c.-146G>T
NM_001408466.1:c.-26G>T
NM_001408468.1:c.-142G>T
NM_001408469.1:c.-26G>T
NM_001408470.1:c.-26G>T
NM_001408472.1:c.116G>T	NP_001395401.1:p.Cys39Phe	missense
NM_001408473.1:c.116G>T	NP_001395402.1:p.Cys39Phe	missense
NM_001408474.1:c.116G>T	NP_001395403.1:p.Cys39Phe	missense
NM_001408475.1:c.116G>T	NP_001395404.1:p.Cys39Phe	missense
NM_001408476.1:c.116G>T	NP_001395405.1:p.Cys39Phe	missense
NM_001408478.1:c.-73G>T
NM_001408479.1:c.-73G>T
NM_001408480.1:c.-73G>T
NM_001408481.1:c.-73G>T
NM_001408482.1:c.-73G>T
NM_001408483.1:c.-73G>T
NM_001408484.1:c.-73G>T
NM_001408485.1:c.-73G>T
NM_001408489.1:c.-73G>T
NM_001408490.1:c.-73G>T
NM_001408491.1:c.-73G>T
NM_001408492.1:c.-189G>T
NM_001408493.1:c.-73G>T
NM_001408494.1:c.116G>T	NP_001395423.1:p.Cys39Phe	missense
NM_001408495.1:c.116G>T	NP_001395424.1:p.Cys39Phe	missense
NM_001408497.1:c.-26G>T
NM_001408499.1:c.-26G>T
NM_001408500.1:c.-26G>T
NM_001408501.1:c.-142G>T
NM_001408502.1:c.-73G>T
NM_001408503.1:c.-26G>T
NM_001408504.1:c.-26G>T
NM_001408505.1:c.-26G>T
NM_001408506.1:c.-73G>T
NM_001408507.1:c.-73G>T
NM_001408508.1:c.-73G>T
NM_001408509.1:c.-73G>T
NM_001408510.1:c.-188G>T
NM_001408512.1:c.-188G>T
NM_001408513.1:c.-73G>T
NM_001408514.1:c.-73G>T
NM_007297.4:c.-8+8273G>T		intron variant
NM_007298.4:c.116G>T	NP_009229.2:p.Cys39Phe	missense
NM_007299.4:c.116G>T	NP_009230.2:p.Cys39Phe	missense
NM_007300.4:c.116G>T	NP_009231.2:p.Cys39Phe	missense
NM_007304.2:c.116G>T	NP_009235.2:p.Cys39Phe	missense
NR_027676.2:n.318G>T		non-coding transcript variant
NC_000017.11:g.43115744C>A
NC_000017.10:g.41267761C>A
NG_005905.2:g.102240G>T
LRG_292:g.102240G>T
LRG_292t1:c.116G>T	LRG_292p1:p.Cys39Phe

... more HGVS ... less HGVS

Protein change

C39F

Other names

235G>T

Canonical SPDI

NC_000017.11:43115743:C:A

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.116G>T, a MISSENSE variant, produced a function score of -2.32, 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

ClinGen: CA000773 dbSNP: rs80357498 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	Pathogenic (4)	criteria provided, single submitter	Oct 2, 2015	RCV000030974.9
Hereditary breast ovarian cancer syndrome	Likely pathogenic (1)	criteria provided, single submitter	Nov 22, 2023	RCV000206829.10
Breast and/or ovarian cancer	Likely pathogenic (1)	criteria provided, single submitter	Jan 12, 2022	RCV001798024.4
Hereditary cancer-predisposing syndrome	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Mar 7, 2022	RCV000509711.7

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 (Nov 22, 2023)	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: SCV000259445.7 First in ClinVar: Jan 31, 2016 Last updated: Feb 28, 2024	Publications: PubMed (13) PubMed: 28888541‚ 29446198‚ 30209399‚ 9808526‚ 11320250‚ 12827452‚ 19543972‚ 21725363‚ 21922593‚ 21990134‚ 22843421‚ 23161852‚ 24489791 Comment: This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 39 of the BRCA1 protein … (more) This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 39 of the BRCA1 protein (p.Cys39Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with increased risk of breast and/or ovarian cancer (PMID: 28888541, 29446198). ClinVar contains an entry for this variant (Variation ID: 37393). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). This variant disrupts the p.Cys39 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9808526, 11320250, 12827452, 19543972, 21725363, 21922593, 21990134, 22843421, 23161852, 24489791). 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. (less)
Pathogenic (Oct 02, 2015)	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: germline	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge Accession: SCV000324975.4 First in ClinVar: Sep 27, 2014 Last updated: Dec 11, 2022
Pathogenic (Mar 07, 2022)	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: SCV004361135.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 25823446‚ 29446198‚ 30209399‚ 30219179‚ 33278427 Comment: This missense variant replaces cysteine with phenylalanine at codon 39 in the RING domain of the BRCA1 protein. Computational prediction suggests that this variant may … (more) This missense variant replaces cysteine with phenylalanine at codon 39 in the RING domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this mutant protein has decreased ubiquitin protein ligase activity and is deficient in BARD1 binding, and is predicted to be non-functional for homology-directed DNA repair (PMID: 25823446, 30219179). This variant has been reported to be loss-of-function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in individuals affected with breast cancer (PMID: 33278427), and has been identified in one family among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Different variants affecting the same codon, c.115T>A (p.Cys39Ser), c.115T>C (p.Cys39Arg), c.115T>G (p.Cys39Gly), c.116G>A (p.Cys39Tyr), and c.117T>G (p.Cys39Trp) are considered to be disease-causing (ClinVar variation ID: 54151, 54152, 54153, 37392, 267497), supporting that the cysteine at this position is important for protein function. Based on the available evidence, this variant is classified as Pathogenic. (less)
Likely pathogenic (Jan 12, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast and/or ovarian cancer Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV002043419.2 First in ClinVar: Dec 29, 2021 Last updated: Mar 11, 2023	Publications: PubMed (1) PubMed: 25741868
Pathogenic (May 25, 2021)	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: SCV000607989.5 First in ClinVar: Oct 23, 2017 Last updated: May 01, 2024	Publications: PubMed (3) PubMed: 25823446‚ 29446198‚ 30209399 Comment: The p.C39F variant (also known as c.116G>T), located in coding exon 2 of the BRCA1 gene, results from a G to T substitution at nucleotide … (more) The p.C39F variant (also known as c.116G>T), located in coding exon 2 of the BRCA1 gene, results from a G to T substitution at nucleotide position 116. The cysteine at codon 39 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This nucleotide substitution was non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222), and demonstrated impaired BARD1 binding and E3 Ubiquitin Ligase activity (Starita LM et al. Genetics, 2015 Jun;200:413-22). Additionally, codon 39 is located in a critical region of the BRCA1 protein RING domain. Multiple alterations at this codon, including p.C39R, p.C39Y, and p.C39S have been shown to alter the structure of the RING domain and negatively impact protein function and binding (Ruffner H et al. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5134-9; Brzovic PS et al. Proc Natl Acad Sci USA. 2003 May;100(10):5646-51; Ransburgh DJ et al. Cancer Res. 2010 Feb 1;70(3):988-95; Sweet K et al. Breast Cancer Res Treat. 2010 Feb;119(3):737-43). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Pathogenic (Dec 20, 2010)	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: SCV000053565.3 First in ClinVar: Apr 04, 2013 Last updated: Sep 27, 2014
Likely pathogenic (Mar 02, 2020)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: yes Allele origin: germline	BRCAlab, Lund University Accession: SCV004244194.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
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: SCV001242368.1 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:-2.32092314101715

Comment:

This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 39 of the BRCA1 protein (p.Cys39Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with increased risk of breast and/or ovarian cancer (PMID: 28888541, 29446198). ClinVar contains an entry for this variant (Variation ID: 37393). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 30209399). This variant disrupts the p.Cys39 amino acid residue in BRCA1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9808526, 11320250, 12827452, 19543972, 21725363, 21922593, 21990134, 22843421, 23161852, 24489791). 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.

Comment:

This missense variant replaces cysteine with phenylalanine at codon 39 in the RING domain of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have shown that this mutant protein has decreased ubiquitin protein ligase activity and is deficient in BARD1 binding, and is predicted to be non-functional for homology-directed DNA repair (PMID: 25823446, 30219179). This variant has been reported to be loss-of-function in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in individuals affected with breast cancer (PMID: 33278427), and has been identified in one family among the CIMBA participants (PMID: 29446198) (https://cimba.ccge.medschl.cam.ac.uk/). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Different variants affecting the same codon, c.115T>A (p.Cys39Ser), c.115T>C (p.Cys39Arg), c.115T>G (p.Cys39Gly), c.116G>A (p.Cys39Tyr), and c.117T>G (p.Cys39Trp) are considered to be disease-causing (ClinVar variation ID: 54151, 54152, 54153, 37392, 267497), supporting that the cysteine at this position is important for protein function. Based on the available evidence, this variant is classified as Pathogenic.

Comment:

The p.C39F variant (also known as c.116G>T), located in coding exon 2 of the BRCA1 gene, results from a G to T substitution at nucleotide position 116. The cysteine at codon 39 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). This nucleotide substitution was non-functional in a high-throughput, genome editing, haploid cell survival assay (Findlay GM et al. Nature, 2018 10;562:217-222), and demonstrated impaired BARD1 binding and E3 Ubiquitin Ligase activity (Starita LM et al. Genetics, 2015 Jun;200:413-22). Additionally, codon 39 is located in a critical region of the BRCA1 protein RING domain. Multiple alterations at this codon, including p.C39R, p.C39Y, and p.C39S have been shown to alter the structure of the RING domain and negatively impact protein function and binding (Ruffner H et al. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5134-9; Brzovic PS et al. Proc Natl Acad Sci USA. 2003 May;100(10):5646-51; Ransburgh DJ et al. Cancer Res. 2010 Feb 1;70(3):988-95; Sweet K et al. Breast Cancer Res Treat. 2010 Feb;119(3):737-43). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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:-2.32092314101715	Brotman Baty Institute, University of Washington Accession: SCV001242368.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.116G>T, a MISSENSE variant, produced a function score of -2.32, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.116G>T, a MISSENSE variant, produced a function score of -2.32, 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
BRCA1 and BRCA2 truncating mutations and variants of unknown significance in Egyptian female breast cancer patients.	AbdelHamid SG	Clinica chimica acta; international journal of clinical chemistry	2021	PMID: 33278427
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
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.	Rebbeck TR	Human mutation	2018	PMID: 29446198
Frequency of mutations in a large series of clinically ascertained ovarian cancer cases tested on multi-gene panels compared to reference controls.	Lilyquist J	Gynecologic oncology	2017	PMID: 28888541
Massively Parallel Functional Analysis of BRCA1 RING Domain Variants.	Starita LM	Genetics	2015	PMID: 25823446
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868
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
Mechanisms of BRCA1 tumor suppression.	Silver DP	Cancer discovery	2012	PMID: 22843421
A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS).	Lindor NM	Human mutation	2012	PMID: 21990134
Functional differences among BRCA1 missense mutations in the control of centrosome duplication.	Kais Z	Oncogene	2012	PMID: 21725363
Assessment of human Nter and Cter BRCA1 mutations using growth and localization assays in yeast.	Millot GA	Human mutation	2011	PMID: 21922593
Characterization of BRCA1 ring finger variants of uncertain significance.	Sweet K	Breast cancer research and treatment	2010	PMID: 19543972
A mutation analysis of the BRCA1 gene in 140 families from southeast France with a history of breast and/or ovarian cancer.	Rostagno P	Journal of human genetics	2003	PMID: 12827452
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
Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer.	Santarosa M	International journal of cancer	1998	PMID: 9808526
https://sge.gs.washington.edu/BRCA1/	-	-	-	-
click to load more click to collapse

Text-mined citations for rs80357498 ...

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.116G>T (p.Cys39Phe)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80357498 ...