Variant chr17-43169893-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001408458.1(BRCA1):c.-62+233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 427,392 control chromosomes in the GnomAD database, including 194,854 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.89 ( 62594 hom., cov: 31)

Exomes 𝑓: 0.98 ( 132260 hom. )

Consequence

BRCA1
NM_001408458.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.318

Variant links:

Genes affected

ENSG00000267002 (HGNC:):

ENSG00000267002 links:

BRCA1 (HGNC:1100): (BRCA1 DNA repair associated) This gene encodes a 190 kD nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The BRCA1 gene contains 22 exons spanning about 110 kb of DNA. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2020]

BRCA1 links:

BRCA1P1 (HGNC:28470): (BRCA1 pseudogene 1)

BRCA1P1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
BRCA1	NM_001408458.1 link	c.-62+233G>A	intron_variant	NP_001395387.1
BRCA1P1		n.43169893C>T	intragenic_variant
LOC101929767	NR_110868.1 link	n.278+233G>A	intron_variant
LOC124900391	XR_007065760.1 link	n.549+523G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
ENSG00000267002	ENST00000590740.2 link	n.278+233G>A	intron_variant		1
BRCA1	ENST00000634433.2 link	c.-20+233G>A	intron_variant		5	ENSP00000489431.2	A0A0U1RRA9
ENSG00000267340	ENST00000589047.1 link	n.185G>A	non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.894

AC:

135982

AN:

152056

Hom.:

62579

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.971

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.934

Gnomad NFE

AF:

0.991

Gnomad OTH

AF:

0.925

GnomAD4 exome

AF:

0.979

AC:

269347

AN:

275218

Hom.:

132260

Cov.:

AF XY:

0.980

AC XY:

155731

AN XY:

158950

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.980

Gnomad4 ASJ exome

AF:

0.995

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.973

Gnomad4 FIN exome

AF:

0.999

Gnomad4 NFE exome

AF:

0.992

Gnomad4 OTH exome

AF:

0.973

GnomAD4 genome

AF:

0.894

AC:

136037

AN:

152174

Hom.:

62594

Cov.:

AF XY:

0.897

AC XY:

66758

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.962

Gnomad4 ASJ

AF:

0.995

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.971

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.991

Gnomad4 OTH

AF:

0.926

Alfa

AF:

0.979

Hom.:

113945

Bravo

AF:

0.880

Asia WGS

AF:

0.959

AC:

3335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.1

DANN

Benign

0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over