15-40695527-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.-3+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 152,258 control chromosomes in the GnomAD database, including 780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (779 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.288

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=-0.8).
• BP6: Variant 15-40695527-C-T is Benign according to our data. Variant chr15-40695527-C-T is described in ClinVar as [Benign]. Clinvar id is 1261176.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.-3+102C>T		intron_variant		ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.-3+102C>T		intron_variant		1	NM_002875.5	P1

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12593 AN: 152020 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0646

GnomAD4 exome AF: 0.144 AC: 17 AN: 118 Hom.: 1 Cov.: 0 AF XY: 0.174 AC XY: 15 AN XY: 86

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0828 AC: 12593 AN: 152140 Hom.: 779 Cov.: 32 AF XY: 0.0823 AC XY: 6123 AN XY: 74398

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.105 Hom.: 1147

Bravo AF: 0.0720

Asia WGS AF: 0.0250 AC: 86 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

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.6
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: rs3092981; hg19: chr15-40987725;