17-43125988-G-GTGT

Position:

• chr17-43125988-G-GTGT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001408458.1(BRCA1):​c.-61-10212_-61-10210dupACA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7886 hom., cov: 0)
• Consequence: BRCA1 NM_001408458.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

Genes affected

NBR2 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRCA1	NM_001408458.1	c.-61-10212_-61-10210dupACA		intron_variant			NP_001395387.1
NBR2	NR_003108.2	n.214+220_214+222dupGTT		intron_variant
NBR2	NR_138145.1	n.214+220_214+222dupGTT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NBR2	ENST00000356906.7	n.131+220_131+222dupGTT		intron_variant		1
BRCA1	ENST00000634433.2	c.-19-1876_-19-1874dupACA		intron_variant		5		ENSP00000489431.2
NBR2	ENST00000460115.5	n.161+220_161+222dupGTT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47977 AN: 151752 Hom.: 7880 Cov.: 0

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.316 AC: 48011 AN: 151870 Hom.: 7886 Cov.: 0 AF XY: 0.322 AC XY: 23925 AN XY: 74200

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.402

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.337

Alfa AF: 0.314 Hom.: 803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8176071; hg19: chr17-41278005;