chr15-40732105-T-C

Position:

• chr15-40732105-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002875.5(RAD51):​c.*927T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 200,692 control chromosomes in the GnomAD database, including 27,437 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 0.50 (19566 hom., cov: 32)
  • Exomes 𝑓: 0.55 (7871 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.*927T>C		3_prime_UTR_variant	10/10	ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.*927T>C		3_prime_UTR_variant	10/10	1	NM_002875.5	P1
RAD51	ENST00000645673.2	c.*927T>C		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75255 AN: 151868 Hom.: 19553 Cov.: 32

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.552 AC: 26873 AN: 48706 Hom.: 7871 Cov.: 0 AF XY: 0.552 AC XY: 12474 AN XY: 22584

Gnomad4 AFR exome AF: 0.365

Gnomad4 AMR exome AF: 0.646

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.847

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.495 AC: 75292 AN: 151986 Hom.: 19566 Cov.: 32 AF XY: 0.507 AC XY: 37633 AN XY: 74280

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.497

Alfa AF: 0.495 Hom.: 2746

Bravo AF: 0.493

Asia WGS AF: 0.716 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11855560; hg19: chr15-41024303;