rs4417527

chr15-40729082-C-Gchr15-40729082-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002875.5(RAD51):c.644+258C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,908 control chromosomes in the GnomAD database, including 4,766 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (4766 hom., cov: 31)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-40729082-C-G is Benign according to our data. Variant chr15-40729082-C-G is described in ClinVar as [Benign]. Clinvar id is 1181406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.644+258C>G		intron_variant		ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.644+258C>G		intron_variant		1	NM_002875.5	P1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33763 AN: 151790 Hom.: 4749 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.222 AC: 33798 AN: 151908 Hom.: 4766 Cov.: 31 AF XY: 0.229 AC XY: 16996 AN XY: 74250

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.226

Alfa AF: 0.179 Hom.: 358

Bravo AF: 0.246

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.79

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: rs4417527; hg19: chr15-41021280;