rs11852786

Positions:

• chr15-40732310-G-C
• chr15-40732310-G-T

Variant summary

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

The NM_002875.5(RAD51):​c.*1132G>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 0.549 in 168,062 control chromosomes in the GnomAD database, including 25,930 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 0.55 (23077 hom., cov: 29)
  • Exomes 𝑓: 0.56 (2853 hom.)
• Consequence: RAD51 NM_002875.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-1.0).
• 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	Protein	UniProt
RAD51	NM_002875.5	c.*1132G>C		3_prime_UTR_variant	10/10	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.*1132G>C		3_prime_UTR_variant	10/10	1	NM_002875.5	ENSP00000267868	P1
RAD51	ENST00000645673.2	c.*1132G>C		3_prime_UTR_variant	10/10			ENSP00000493712

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82695 AN: 151188 Hom.: 23047 Cov.: 29

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.564 AC: 9460 AN: 16768 Hom.: 2853 Cov.: 0 AF XY: 0.561 AC XY: 4333 AN XY: 7720

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.627

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.541

GnomAD4 genome AF: 0.547 AC: 82777 AN: 151294 Hom.: 23077 Cov.: 29 AF XY: 0.556 AC XY: 41057 AN XY: 73852

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.597

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.530

Alfa AF: 0.525 Hom.: 2581

Bravo AF: 0.552

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.39

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: rs11852786; hg19: chr15-41024508;