VCV000125777.17 - ClinVar

NM_007294.4(BRCA1):c.5152+6T>C

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.

(7)

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
Pathogenic(1); Likely pathogenic(2); Uncertain significance(2)

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.5152+6T>C

Variation ID: 125777 Accession: VCV000125777.17

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.31 17: 43063868 (GRCh38) [ NCBI UCSC ] 17: 41215885 (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 4, 2014	May 1, 2024	Feb 7, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.5152+6T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001407571.1:c.4939+6T>C		intron variant
NM_001407581.1:c.5218+6T>C		intron variant
NM_001407582.1:c.5218+6T>C		intron variant
NM_001407583.1:c.5215+6T>C		intron variant
NM_001407585.1:c.5215+6T>C		intron variant
NM_001407587.1:c.5215+6T>C		intron variant
NM_001407590.1:c.5212+6T>C		intron variant
NM_001407591.1:c.5212+6T>C		intron variant
NM_001407593.1:c.5152+6T>C		intron variant
NM_001407594.1:c.5152+6T>C		intron variant
NM_001407596.1:c.5152+6T>C		intron variant
NM_001407597.1:c.5152+6T>C		intron variant
NM_001407598.1:c.5152+6T>C		intron variant
NM_001407602.1:c.5152+6T>C		intron variant
NM_001407603.1:c.5152+6T>C		intron variant
NM_001407605.1:c.5152+6T>C		intron variant
NM_001407610.1:c.5149+6T>C		intron variant
NM_001407611.1:c.5149+6T>C		intron variant
NM_001407612.1:c.5149+6T>C		intron variant
NM_001407613.1:c.5149+6T>C		intron variant
NM_001407614.1:c.5149+6T>C		intron variant
NM_001407615.1:c.5149+6T>C		intron variant
NM_001407616.1:c.5149+6T>C		intron variant
NM_001407617.1:c.5149+6T>C		intron variant
NM_001407618.1:c.5149+6T>C		intron variant
NM_001407619.1:c.5149+6T>C		intron variant
NM_001407620.1:c.5149+6T>C		intron variant
NM_001407621.1:c.5149+6T>C		intron variant
NM_001407622.1:c.5149+6T>C		intron variant
NM_001407623.1:c.5149+6T>C		intron variant
NM_001407624.1:c.5149+6T>C		intron variant
NM_001407625.1:c.5149+6T>C		intron variant
NM_001407626.1:c.5149+6T>C		intron variant
NM_001407627.1:c.5146+6T>C		intron variant
NM_001407628.1:c.5146+6T>C		intron variant
NM_001407629.1:c.5146+6T>C		intron variant
NM_001407630.1:c.5146+6T>C		intron variant
NM_001407631.1:c.5146+6T>C		intron variant
NM_001407632.1:c.5146+6T>C		intron variant
NM_001407633.1:c.5146+6T>C		intron variant
NM_001407634.1:c.5146+6T>C		intron variant
NM_001407635.1:c.5146+6T>C		intron variant
NM_001407636.1:c.5146+6T>C		intron variant
NM_001407637.1:c.5146+6T>C		intron variant
NM_001407638.1:c.5146+6T>C		intron variant
NM_001407639.1:c.5146+6T>C		intron variant
NM_001407640.1:c.5146+6T>C		intron variant
NM_001407641.1:c.5146+6T>C		intron variant
NM_001407642.1:c.5146+6T>C		intron variant
NM_001407644.1:c.5143+6T>C		intron variant
NM_001407645.1:c.5143+6T>C		intron variant
NM_001407646.1:c.5140+6T>C		intron variant
NM_001407647.1:c.5137+6T>C		intron variant
NM_001407648.1:c.5095+6T>C		intron variant
NM_001407649.1:c.5092+6T>C		intron variant
NM_001407652.1:c.5075-495T>C		intron variant
NM_001407653.1:c.5074+6T>C		intron variant
NM_001407654.1:c.5074+6T>C		intron variant
NM_001407655.1:c.5074+6T>C		intron variant
NM_001407656.1:c.5071+6T>C		intron variant
NM_001407657.1:c.5071+6T>C		intron variant
NM_001407658.1:c.5071+6T>C		intron variant
NM_001407659.1:c.5068+6T>C		intron variant
NM_001407660.1:c.5068+6T>C		intron variant
NM_001407661.1:c.5068+6T>C		intron variant
NM_001407662.1:c.5068+6T>C		intron variant
NM_001407663.1:c.5068+6T>C		intron variant
NM_001407664.1:c.5029+6T>C		intron variant
NM_001407665.1:c.5029+6T>C		intron variant
NM_001407666.1:c.5029+6T>C		intron variant
NM_001407667.1:c.5029+6T>C		intron variant
NM_001407668.1:c.5029+6T>C		intron variant
NM_001407669.1:c.5029+6T>C		intron variant
NM_001407670.1:c.5026+6T>C		intron variant
NM_001407671.1:c.5026+6T>C		intron variant
NM_001407672.1:c.5026+6T>C		intron variant
NM_001407673.1:c.5026+6T>C		intron variant
NM_001407674.1:c.5026+6T>C		intron variant
NM_001407675.1:c.5026+6T>C		intron variant
NM_001407676.1:c.5026+6T>C		intron variant
NM_001407677.1:c.5026+6T>C		intron variant
NM_001407678.1:c.5026+6T>C		intron variant
NM_001407679.1:c.5026+6T>C		intron variant
NM_001407680.1:c.5026+6T>C		intron variant
NM_001407681.1:c.5023+6T>C		intron variant
NM_001407682.1:c.5023+6T>C		intron variant
NM_001407683.1:c.5023+6T>C		intron variant
NM_001407684.1:c.5152+6T>C		intron variant
NM_001407685.1:c.5023+6T>C		intron variant
NM_001407686.1:c.5023+6T>C		intron variant
NM_001407687.1:c.5023+6T>C		intron variant
NM_001407688.1:c.5023+6T>C		intron variant
NM_001407689.1:c.5023+6T>C		intron variant
NM_001407690.1:c.5020+6T>C		intron variant
NM_001407691.1:c.5020+6T>C		intron variant
NM_001407692.1:c.5011+6T>C		intron variant
NM_001407694.1:c.5011+6T>C		intron variant
NM_001407695.1:c.5011+6T>C		intron variant
NM_001407696.1:c.5011+6T>C		intron variant
NM_001407697.1:c.5011+6T>C		intron variant
NM_001407698.1:c.5011+6T>C		intron variant
NM_001407724.1:c.5011+6T>C		intron variant
NM_001407725.1:c.5011+6T>C		intron variant
NM_001407726.1:c.5011+6T>C		intron variant
NM_001407727.1:c.5011+6T>C		intron variant
NM_001407728.1:c.5011+6T>C		intron variant
NM_001407729.1:c.5011+6T>C		intron variant
NM_001407730.1:c.5011+6T>C		intron variant
NM_001407731.1:c.5011+6T>C		intron variant
NM_001407732.1:c.5008+6T>C		intron variant
NM_001407733.1:c.5008+6T>C		intron variant
NM_001407734.1:c.5008+6T>C		intron variant
NM_001407735.1:c.5008+6T>C		intron variant
NM_001407736.1:c.5008+6T>C		intron variant
NM_001407737.1:c.5008+6T>C		intron variant
NM_001407738.1:c.5008+6T>C		intron variant
NM_001407739.1:c.5008+6T>C		intron variant
NM_001407740.1:c.5008+6T>C		intron variant
NM_001407741.1:c.5008+6T>C		intron variant
NM_001407742.1:c.5008+6T>C		intron variant
NM_001407743.1:c.5008+6T>C		intron variant
NM_001407744.1:c.5008+6T>C		intron variant
NM_001407745.1:c.5008+6T>C		intron variant
NM_001407746.1:c.5008+6T>C		intron variant
NM_001407747.1:c.5008+6T>C		intron variant
NM_001407748.1:c.5008+6T>C		intron variant
NM_001407749.1:c.5008+6T>C		intron variant
NM_001407750.1:c.5008+6T>C		intron variant
NM_001407751.1:c.5008+6T>C		intron variant
NM_001407752.1:c.5008+6T>C		intron variant
NM_001407838.1:c.5005+6T>C		intron variant
NM_001407839.1:c.5005+6T>C		intron variant
NM_001407841.1:c.5005+6T>C		intron variant
NM_001407842.1:c.5005+6T>C		intron variant
NM_001407843.1:c.5005+6T>C		intron variant
NM_001407844.1:c.5005+6T>C		intron variant
NM_001407845.1:c.5005+6T>C		intron variant
NM_001407846.1:c.5005+6T>C		intron variant
NM_001407847.1:c.5005+6T>C		intron variant
NM_001407848.1:c.5005+6T>C		intron variant
NM_001407849.1:c.5005+6T>C		intron variant
NM_001407850.1:c.5005+6T>C		intron variant
NM_001407851.1:c.5005+6T>C		intron variant
NM_001407852.1:c.5005+6T>C		intron variant
NM_001407853.1:c.5005+6T>C		intron variant
NM_001407854.1:c.5152+6T>C		intron variant
NM_001407858.1:c.5149+6T>C		intron variant
NM_001407859.1:c.5149+6T>C		intron variant
NM_001407860.1:c.5149+6T>C		intron variant
NM_001407861.1:c.5146+6T>C		intron variant
NM_001407862.1:c.4951+6T>C		intron variant
NM_001407863.1:c.4949-495T>C		intron variant
NM_001407874.1:c.4945+6T>C		intron variant
NM_001407875.1:c.4945+6T>C		intron variant
NM_001407879.1:c.4942+6T>C		intron variant
NM_001407881.1:c.4942+6T>C		intron variant
NM_001407882.1:c.4942+6T>C		intron variant
NM_001407884.1:c.4942+6T>C		intron variant
NM_001407885.1:c.4942+6T>C		intron variant
NM_001407886.1:c.4942+6T>C		intron variant
NM_001407887.1:c.4942+6T>C		intron variant
NM_001407889.1:c.4942+6T>C		intron variant
NM_001407894.1:c.4939+6T>C		intron variant
NM_001407895.1:c.4939+6T>C		intron variant
NM_001407896.1:c.4939+6T>C		intron variant
NM_001407897.1:c.4939+6T>C		intron variant
NM_001407898.1:c.4939+6T>C		intron variant
NM_001407899.1:c.4939+6T>C		intron variant
NM_001407900.1:c.4939+6T>C		intron variant
NM_001407902.1:c.4939+6T>C		intron variant
NM_001407904.1:c.4939+6T>C		intron variant
NM_001407906.1:c.4939+6T>C		intron variant
NM_001407907.1:c.4939+6T>C		intron variant
NM_001407908.1:c.4939+6T>C		intron variant
NM_001407909.1:c.4939+6T>C		intron variant
NM_001407910.1:c.4939+6T>C		intron variant
NM_001407915.1:c.4936+6T>C		intron variant
NM_001407916.1:c.4936+6T>C		intron variant
NM_001407917.1:c.4936+6T>C		intron variant
NM_001407918.1:c.4936+6T>C		intron variant
NM_001407919.1:c.5029+6T>C		intron variant
NM_001407920.1:c.4888+6T>C		intron variant
NM_001407921.1:c.4888+6T>C		intron variant
NM_001407922.1:c.4888+6T>C		intron variant
NM_001407923.1:c.4888+6T>C		intron variant
NM_001407924.1:c.4888+6T>C		intron variant
NM_001407925.1:c.4888+6T>C		intron variant
NM_001407926.1:c.4888+6T>C		intron variant
NM_001407927.1:c.4885+6T>C		intron variant
NM_001407928.1:c.4885+6T>C		intron variant
NM_001407929.1:c.4885+6T>C		intron variant
NM_001407930.1:c.4885+6T>C		intron variant
NM_001407931.1:c.4885+6T>C		intron variant
NM_001407932.1:c.4885+6T>C		intron variant
NM_001407933.1:c.4885+6T>C		intron variant
NM_001407934.1:c.4882+6T>C		intron variant
NM_001407935.1:c.4882+6T>C		intron variant
NM_001407936.1:c.4882+6T>C		intron variant
NM_001407937.1:c.5029+6T>C		intron variant
NM_001407938.1:c.5029+6T>C		intron variant
NM_001407939.1:c.5026+6T>C		intron variant
NM_001407940.1:c.5026+6T>C		intron variant
NM_001407941.1:c.5023+6T>C		intron variant
NM_001407942.1:c.5011+6T>C		intron variant
NM_001407943.1:c.5008+6T>C		intron variant
NM_001407944.1:c.5008+6T>C		intron variant
NM_001407945.1:c.5008+6T>C		intron variant
NM_001407946.1:c.4819+6T>C		intron variant
NM_001407947.1:c.4819+6T>C		intron variant
NM_001407948.1:c.4819+6T>C		intron variant
NM_001407949.1:c.4819+6T>C		intron variant
NM_001407950.1:c.4816+6T>C		intron variant
NM_001407951.1:c.4816+6T>C		intron variant
NM_001407952.1:c.4816+6T>C		intron variant
NM_001407953.1:c.4816+6T>C		intron variant
NM_001407954.1:c.4816+6T>C		intron variant
NM_001407955.1:c.4816+6T>C		intron variant
NM_001407956.1:c.4813+6T>C		intron variant
NM_001407957.1:c.4813+6T>C		intron variant
NM_001407958.1:c.4813+6T>C		intron variant
NM_001407959.1:c.4771+6T>C		intron variant
NM_001407960.1:c.4768+6T>C		intron variant
NM_001407962.1:c.4768+6T>C		intron variant
NM_001407963.1:c.4765+6T>C		intron variant
NM_001407964.1:c.4690+6T>C		intron variant
NM_001407965.1:c.4645+6T>C		intron variant
NM_001407966.1:c.4264+6T>C		intron variant
NM_001407967.1:c.4261+6T>C		intron variant
NM_001407968.1:c.2548+6T>C		intron variant
NM_001407969.1:c.2545+6T>C		intron variant
NM_001407970.1:c.1909+6T>C		intron variant
NM_001407971.1:c.1909+6T>C		intron variant
NM_001407972.1:c.1906+6T>C		intron variant
NM_001407973.1:c.1843+6T>C		intron variant
NM_001407974.1:c.1843+6T>C		intron variant
NM_001407975.1:c.1843+6T>C		intron variant
NM_001407976.1:c.1843+6T>C		intron variant
NM_001407977.1:c.1843+6T>C		intron variant
NM_001407978.1:c.1843+6T>C		intron variant
NM_001407979.1:c.1840+6T>C		intron variant
NM_001407980.1:c.1840+6T>C		intron variant
NM_001407981.1:c.1840+6T>C		intron variant
NM_001407982.1:c.1840+6T>C		intron variant
NM_001407983.1:c.1840+6T>C		intron variant
NM_001407984.1:c.1840+6T>C		intron variant
NM_001407985.1:c.1840+6T>C		intron variant
NM_001407986.1:c.1840+6T>C		intron variant
NM_001407990.1:c.1840+6T>C		intron variant
NM_001407991.1:c.1840+6T>C		intron variant
NM_001407992.1:c.1840+6T>C		intron variant
NM_001407993.1:c.1840+6T>C		intron variant
NM_001408392.1:c.1837+6T>C		intron variant
NM_001408396.1:c.1837+6T>C		intron variant
NM_001408397.1:c.1837+6T>C		intron variant
NM_001408398.1:c.1837+6T>C		intron variant
NM_001408399.1:c.1837+6T>C		intron variant
NM_001408400.1:c.1837+6T>C		intron variant
NM_001408401.1:c.1837+6T>C		intron variant
NM_001408402.1:c.1837+6T>C		intron variant
NM_001408403.1:c.1837+6T>C		intron variant
NM_001408404.1:c.1837+6T>C		intron variant
NM_001408406.1:c.1834+6T>C		intron variant
NM_001408407.1:c.1834+6T>C		intron variant
NM_001408408.1:c.1834+6T>C		intron variant
NM_001408409.1:c.1831+6T>C		intron variant
NM_001408410.1:c.1768+6T>C		intron variant
NM_001408411.1:c.1765+6T>C		intron variant
NM_001408412.1:c.1762+6T>C		intron variant
NM_001408413.1:c.1762+6T>C		intron variant
NM_001408414.1:c.1762+6T>C		intron variant
NM_001408415.1:c.1762+6T>C		intron variant
NM_001408416.1:c.1762+6T>C		intron variant
NM_001408418.1:c.1726+6T>C		intron variant
NM_001408419.1:c.1726+6T>C		intron variant
NM_001408420.1:c.1726+6T>C		intron variant
NM_001408421.1:c.1723+6T>C		intron variant
NM_001408422.1:c.1723+6T>C		intron variant
NM_001408423.1:c.1723+6T>C		intron variant
NM_001408424.1:c.1723+6T>C		intron variant
NM_001408425.1:c.1720+6T>C		intron variant
NM_001408426.1:c.1720+6T>C		intron variant
NM_001408427.1:c.1720+6T>C		intron variant
NM_001408428.1:c.1720+6T>C		intron variant
NM_001408429.1:c.1720+6T>C		intron variant
NM_001408430.1:c.1720+6T>C		intron variant
NM_001408431.1:c.1720+6T>C		intron variant
NM_001408432.1:c.1717+6T>C		intron variant
NM_001408433.1:c.1717+6T>C		intron variant
NM_001408434.1:c.1717+6T>C		intron variant
NM_001408435.1:c.1717+6T>C		intron variant
NM_001408436.1:c.1717+6T>C		intron variant
NM_001408437.1:c.1717+6T>C		intron variant
NM_001408438.1:c.1717+6T>C		intron variant
NM_001408439.1:c.1717+6T>C		intron variant
NM_001408440.1:c.1717+6T>C		intron variant
NM_001408441.1:c.1717+6T>C		intron variant
NM_001408442.1:c.1717+6T>C		intron variant
NM_001408443.1:c.1717+6T>C		intron variant
NM_001408444.1:c.1717+6T>C		intron variant
NM_001408445.1:c.1714+6T>C		intron variant
NM_001408446.1:c.1714+6T>C		intron variant
NM_001408447.1:c.1714+6T>C		intron variant
NM_001408448.1:c.1714+6T>C		intron variant
NM_001408450.1:c.1714+6T>C		intron variant
NM_001408451.1:c.1708+6T>C		intron variant
NM_001408452.1:c.1702+6T>C		intron variant
NM_001408453.1:c.1702+6T>C		intron variant
NM_001408454.1:c.1702+6T>C		intron variant
NM_001408455.1:c.1702+6T>C		intron variant
NM_001408456.1:c.1702+6T>C		intron variant
NM_001408457.1:c.1702+6T>C		intron variant
NM_001408458.1:c.1699+6T>C		intron variant
NM_001408459.1:c.1699+6T>C		intron variant
NM_001408460.1:c.1699+6T>C		intron variant
NM_001408461.1:c.1699+6T>C		intron variant
NM_001408462.1:c.1699+6T>C		intron variant
NM_001408463.1:c.1699+6T>C		intron variant
NM_001408464.1:c.1699+6T>C		intron variant
NM_001408465.1:c.1699+6T>C		intron variant
NM_001408466.1:c.1699+6T>C		intron variant
NM_001408467.1:c.1699+6T>C		intron variant
NM_001408468.1:c.1696+6T>C		intron variant
NM_001408469.1:c.1696+6T>C		intron variant
NM_001408470.1:c.1696+6T>C		intron variant
NM_001408472.1:c.1840+6T>C		intron variant
NM_001408473.1:c.1837+6T>C		intron variant
NM_001408474.1:c.1642+6T>C		intron variant
NM_001408475.1:c.1639+6T>C		intron variant
NM_001408476.1:c.1639+6T>C		intron variant
NM_001408478.1:c.1633+6T>C		intron variant
NM_001408479.1:c.1633+6T>C		intron variant
NM_001408480.1:c.1633+6T>C		intron variant
NM_001408481.1:c.1630+6T>C		intron variant
NM_001408482.1:c.1630+6T>C		intron variant
NM_001408483.1:c.1630+6T>C		intron variant
NM_001408484.1:c.1630+6T>C		intron variant
NM_001408485.1:c.1630+6T>C		intron variant
NM_001408489.1:c.1630+6T>C		intron variant
NM_001408490.1:c.1630+6T>C		intron variant
NM_001408491.1:c.1630+6T>C		intron variant
NM_001408492.1:c.1627+6T>C		intron variant
NM_001408493.1:c.1627+6T>C		intron variant
NM_001408494.1:c.1603+6T>C		intron variant
NM_001408495.1:c.1597+6T>C		intron variant
NM_001408496.1:c.1579+6T>C		intron variant
NM_001408497.1:c.1579+6T>C		intron variant
NM_001408498.1:c.1579+6T>C		intron variant
NM_001408499.1:c.1579+6T>C		intron variant
NM_001408500.1:c.1579+6T>C		intron variant
NM_001408501.1:c.1579+6T>C		intron variant
NM_001408502.1:c.1576+6T>C		intron variant
NM_001408503.1:c.1576+6T>C		intron variant
NM_001408504.1:c.1576+6T>C		intron variant
NM_001408505.1:c.1573+6T>C		intron variant
NM_001408506.1:c.1516+6T>C		intron variant
NM_001408507.1:c.1513+6T>C		intron variant
NM_001408508.1:c.1504+6T>C		intron variant
NM_001408509.1:c.1501+6T>C		intron variant
NM_001408510.1:c.1462+6T>C		intron variant
NM_001408511.1:c.1459+6T>C		intron variant
NM_001408512.1:c.1339+6T>C		intron variant
NM_001408513.1:c.1312+6T>C		intron variant
NM_001408514.1:c.916+6T>C		intron variant
NM_007297.4:c.5011+6T>C		intron variant
NM_007298.4:c.1840+6T>C		intron variant
NM_007299.4:c.1840+6T>C		intron variant
NM_007300.4:c.5215+6T>C		intron variant
NC_000017.11:g.43063868A>G
NC_000017.10:g.41215885A>G
NG_005905.2:g.154116T>C
LRG_292:g.154116T>C
LRG_292t1:c.5152+6T>C
U14680.1:n.5271+6T>C

... more HGVS ... less HGVS

Protein change

Other names

IVS18+6T>C

Canonical SPDI

NC_000017.11:43063867:A:G

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.5152+6T>C, a SPLICE REGION variant, produced a function score of -1.4, 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

Breast Cancer Information Core (BIC) (BRCA1): 5271+6&base_change=T to C ClinGen: CA003291 dbSNP: rs80358074 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	13044	14850

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 (4)	criteria provided, conflicting classifications	Aug 1, 2020	RCV000112523.7
Hereditary breast ovarian cancer syndrome	Uncertain significance (1)	criteria provided, single submitter	Jun 20, 2022	RCV000687321.9
Hereditary cancer-predisposing syndrome	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Feb 7, 2023	RCV001525568.8

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.
Uncertain significance (Apr 03, 2017)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 1 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000785071.2 First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014
Likely pathogenic (Aug 01, 2020)	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	Kong lab, Department of Laboratory Medicine, National Cancer Center Accession: SCV003923308.1 First in ClinVar: May 27, 2023 Last updated: May 27, 2023	Publications: PubMed (2) PubMed: 32761968‚ 30209399 Comment: The c.5152+6T>C variant in BRCA1 has been detected in a PT51 patient, who was diagnosed with triple-negative breast cancer (TNBC) IDC at 39 years of … (more) The c.5152+6T>C variant in BRCA1 has been detected in a PT51 patient, who was diagnosed with triple-negative breast cancer (TNBC) IDC at 39 years of age. BRCA1 c.5152+6T>C mRNA transcripts were abnormal compared with their corresponding wild-type transcripts (effect on RNA splicing); this variant produced a combined exon 17 and 19 by exon 18 skipping in BRCA1 and was predicted to be an in-frame deletion (26 amino acids: 1692~1717 a.a.) of the BRCA1 C-terminal (BRCT) domain of BRCA1 (Ryu 2020; PMID: 32761968). This variant does not have frequency information in genome databases, including ExAC (http://exac.broadinstitute.org/) and gnomAD (http://gnomad.broadinstitue.org), and has not been reported in the literature. Moreover, BRCA1 c.5152+6T>C was not detected in the 393 healthy female Korean controls (Ryu 2020; PMID: 32761968). By employing a saturation-genome-editing technique based on CRISPR-mediated homology-directed repair, Findlay et al suggested that BRCA1 c.5152+6T>C is a loss-of-function variant (PMID: 30209399). Thus, BRCA1 c.5152+6T>C has been classified as likely pathogenic. (less) Age: 30-39 years Sex: female Ethnicity/Population group: Asia Comment on evidence: Exon 18 (78 bp) skipping between exon 17 and exon 19 was identified by RT-PCR and Sanger sequencing in lymphocyte-derived RNA from PT51 breast cancer … (more) Exon 18 (78 bp) skipping between exon 17 and exon 19 was identified by RT-PCR and Sanger sequencing in lymphocyte-derived RNA from PT51 breast cancer patient. Amino acid sequences of the splice variant (c.5152+6T>C) were aligned using a reference sequence (NP_009225.1) via NCBI BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi). BRCA1 c.5152+6T>C was identified to encode a BRCA1 protein with an in-frame deletion (26 amino acids: 1692~1717a.a.) in the BRCA1 C-terminal (BRCT) domain; this may affect the function of the BRCA1 BRCT domain. (less) Method: Analyzed RNA transcripts from patient samples to compare out-comes via in silico splicing analysis. Total RNA was extracted from peripheral blood lymphocytes using the NucleoSpin RNA Blood Kit (Macherey-Nagel) or from normal tissues using the AllPrep DNA/RNA Mini Kit (Qiagen) according to manufacturer's instructions. Using total RNA (1 μg) as template, cDNA was reverse-transcribed using the Transcriptor First Strand cDNA Synthesis Kit (Roche Life Science) or ReverTra Ace qPCR RT Master Mix (Toyobo), followed by amplification via reverse transcription PCR (RT-PCR). Transcriptional product for intronic variants in BRCA1 (c.5152+6T>C) was obtained and validated by Sanger sequencing.
Uncertain significance (Jun 20, 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: SCV000814884.5 First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024	Publications: PubMed (5) PubMed: 28492532‚ 30209399‚ 32123317‚ 17576681‚ 9536098 Comment: Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains … (more) Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 125777). 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 falls in intron 17 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. It affects a nucleotide within the consensus splice site. Experimental studies have shown that this variant affects BRCA1 function (PMID: 30209399, 32123317). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. (less)
Likely pathogenic (Feb 07, 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: SCV001735726.2 First in ClinVar: Jun 19, 2021 Last updated: Feb 14, 2024	Publications: PubMed (3) PubMed: 30209399‚ 32123317‚ 32761968 Comment: This variant causes a T to C nucleotide substitution at the +6 position of intron 17 of the BRCA1 gene. Multiple splicing prediction tools indicate … (more) This variant causes a T to C nucleotide substitution at the +6 position of intron 17 of the BRCA1 gene. Multiple splicing prediction tools indicate this variant may impair RNA splicing. RNA studies have reported that this variant causes aberrant splicing and in-frame skipping of exon 17 (exon 18 based on the BIC nomenclature) (PMID: 32123317, 32761968). The aberrant transcript is expected to result in nonfunctional protein product with p.Asp1692_Trp1718delinsGly in the BRCT1 domain of the BRCA1 protein. This variant has also been reported to result in the loss of BRCA1 protein function in a haploid cell proliferation assay (PMID: 30209399). Other nucleotide substitutions at the same position, c.5152+6T>A and c.5152+6T>G, are also reported to result in loss of BRCA1 function in the same study (PMID: 30209399). This variant has been observed in an individual with triple-negative breast cancer with family history of ovarian cancer in a second-degree relative (PMID: 32761968) and in an individual with ovarian cancer (Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. (less)
Pathogenic (Dec 27, 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: SCV002641069.3 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (2) PubMed: 30209399‚ 32123317 Comment: The c.5152+6T>C intronic pathogenic mutation results from a T to C substitution 6 nucleotides after coding exon 16 in the BRCA1 gene. Two functional studies … (more) The c.5152+6T>C intronic pathogenic mutation results from a T to C substitution 6 nucleotides after coding exon 16 in the BRCA1 gene. Two functional studies have found that this nucleotide substitution is deleterious (Findlay GM et al. Nature. 2018 10;562:217-222; Wai HA et al. Genet Med. 2020 06;22:1005-1014). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. A close match alteration at the same nucleotide position, BRCA1 c.5152+6T>G, demonstrated abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
Uncertain significance (Nov 25, 2004)	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: SCV000145345.1 First in ClinVar: Apr 04, 2014 Last updated: Apr 04, 2014	Number of individuals with the variant: 1
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: SCV001243638.1 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:-1.39626508303885

Comment:

The c.5152+6T>C variant in BRCA1 has been detected in a PT51 patient, who was diagnosed with triple-negative breast cancer (TNBC) IDC at 39 years of age. BRCA1 c.5152+6T>C mRNA transcripts were abnormal compared with their corresponding wild-type transcripts (effect on RNA splicing); this variant produced a combined exon 17 and 19 by exon 18 skipping in BRCA1 and was predicted to be an in-frame deletion (26 amino acids: 1692~1717 a.a.) of the BRCA1 C-terminal (BRCT) domain of BRCA1 (Ryu 2020; PMID: 32761968). This variant does not have frequency information in genome databases, including ExAC (http://exac.broadinstitute.org/) and gnomAD (http://gnomad.broadinstitue.org), and has not been reported in the literature. Moreover, BRCA1 c.5152+6T>C was not detected in the 393 healthy female Korean controls (Ryu 2020; PMID: 32761968). By employing a saturation-genome-editing technique based on CRISPR-mediated homology-directed repair, Findlay et al suggested that BRCA1 c.5152+6T>C is a loss-of-function variant (PMID: 30209399). Thus, BRCA1 c.5152+6T>C has been classified as likely pathogenic.

Comment:

Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 125777). 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 falls in intron 17 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein. It affects a nucleotide within the consensus splice site. Experimental studies have shown that this variant affects BRCA1 function (PMID: 30209399, 32123317). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

Comment:

This variant causes a T to C nucleotide substitution at the +6 position of intron 17 of the BRCA1 gene. Multiple splicing prediction tools indicate this variant may impair RNA splicing. RNA studies have reported that this variant causes aberrant splicing and in-frame skipping of exon 17 (exon 18 based on the BIC nomenclature) (PMID: 32123317, 32761968). The aberrant transcript is expected to result in nonfunctional protein product with p.Asp1692_Trp1718delinsGly in the BRCT1 domain of the BRCA1 protein. This variant has also been reported to result in the loss of BRCA1 protein function in a haploid cell proliferation assay (PMID: 30209399). Other nucleotide substitutions at the same position, c.5152+6T>A and c.5152+6T>G, are also reported to result in loss of BRCA1 function in the same study (PMID: 30209399). This variant has been observed in an individual with triple-negative breast cancer with family history of ovarian cancer in a second-degree relative (PMID: 32761968) and in an individual with ovarian cancer (Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic.

Comment:

The c.5152+6T>C intronic pathogenic mutation results from a T to C substitution 6 nucleotides after coding exon 16 in the BRCA1 gene. Two functional studies have found that this nucleotide substitution is deleterious (Findlay GM et al. Nature. 2018 10;562:217-222; Wai HA et al. Genet Med. 2020 06;22:1005-1014). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. A close match alteration at the same nucleotide position, BRCA1 c.5152+6T>G, demonstrated abnormal splicing in the set of samples tested (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. 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:-1.39626508303885	Brotman Baty Institute, University of Washington Accession: SCV001243638.1	Publications PubMed (1) Other databases https://sge.gs.washington.edu/BR… Comment: The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5152+6T>C, a SPLICE REGION variant, produced a function score of -1.4, corresponding to a functional classification of … (more) The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5152+6T>C, a SPLICE REGION variant, produced a function score of -1.4, 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
Exon splicing analysis of intronic variants in multigene cancer panel testing for hereditary breast/ovarian cancer.	Ryu JS	Cancer science	2020	PMID: 32761968
Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance.	Wai HA	Genetics in medicine : official journal of the American College of Medical Genetics	2020	PMID: 32123317
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.	Buratti E	Nucleic acids research	2007	PMID: 17576681
Statistical features of human exons and their flanking regions.	Zhang MQ	Human molecular genetics	1998	PMID: 9536098
https://sge.gs.washington.edu/BRCA1/	-	-	-	-

Text-mined citations for rs80358074 ...

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.5152+6T>C

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80358074 ...