chr15-40731680-T-G

Position:

• chr15-40731680-T-G

Variant summary

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

The NM_002875.5(RAD51):​c.*502T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 239,908 control chromosomes in the GnomAD database, including 34,095 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 (19574 hom., cov: 32)
  • Exomes 𝑓: 0.56 (14521 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.*502T>G		3_prime_UTR_variant	10/10	ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.*502T>G		3_prime_UTR_variant	10/10	1	NM_002875.5	P1
RAD51	ENST00000645673.2	c.*502T>G		3_prime_UTR_variant	10/10

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75292 AN: 151854 Hom.: 19561 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.560 AC: 49207 AN: 87936 Hom.: 14521 Cov.: 0 AF XY: 0.561 AC XY: 23470 AN XY: 41826

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.571

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.497

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.496 AC: 75329 AN: 151972 Hom.: 19574 Cov.: 32 AF XY: 0.507 AC XY: 37662 AN XY: 74286

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.497

Alfa AF: 0.471 Hom.: 6352

Bravo AF: 0.494

Asia WGS AF: 0.716 AC: 2489 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs12593359; hg19: chr15-41023878;