rs770929332

chr17-43124745-GTTTTT-Gchr17-43124745-GTTTTT-GTTTT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The ENST00000618469.2(BRCA1):c.-33_-29del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 202,482 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (2 hom.)
• Consequence: BRCA1 ENST00000618469.2 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.182

Genes affected

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 Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 17-43124745-GTTTTT-G is Benign according to our data. Variant chr17-43124745-GTTTTT-G is described in ClinVar as [Likely_benign]. Clinvar id is 254638.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-43124745-GTTTTT-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRCA1	NM_007294.4	c.-20+521_-20+525del		intron_variant		ENST00000357654.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRCA1	ENST00000357654.9	c.-20+521_-20+525del		intron_variant		1	NM_007294.4	P4

Frequencies

GnomAD3 genomes AF: 0.00250 AC: 380 AN: 151902 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000653

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00254 AC: 128 AN: 50462 Hom.: 2 AF XY: 0.00245 AC XY: 68 AN XY: 27808

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.000341

Gnomad4 ASJ exome AF: 0.00433

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00391

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152020 Hom.: 0 Cov.: 31 AF XY: 0.00227 AC XY: 169 AN XY: 74322

Gnomad4 AFR AF: 0.000651

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.00465

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00270 Hom.: 0

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 1 Benign:1

Likely benign, no assertion criteria provided

clinical testing

Department of Medical Genetics, University Hospital of North Norway

May 01, 2016

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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: rs770929332; hg19: chr17-41276762;