NM_002875.5:c.225+1936T>C

Variant names:

• chr15-40703137-T-C
• rs4924496
• NM_002875.5:c.225+1936T>C

Variant summary

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

The NM_002875.5(RAD51):​c.225+1936T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,108 control chromosomes in the GnomAD database, including 29,941 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 0.62 (29941 hom., cov: 32)
• Consequence: RAD51 NM_002875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5	c.225+1936T>C		intron_variant	Intron 3 of 9	ENST00000267868.8	NP_002866.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51	ENST00000267868.8	c.225+1936T>C		intron_variant	Intron 3 of 9	1	NM_002875.5	ENSP00000267868.3
RAD51	ENST00000532743.6	c.225+1936T>C		intron_variant	Intron 3 of 9	2		ENSP00000433924.2
RAD51	ENST00000557850.5	c.225+1936T>C		intron_variant	Intron 3 of 7	2		ENSP00000454176.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94409 AN: 151990 Hom.: 29891 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.621 AC: 94523 AN: 152108 Hom.: 29941 Cov.: 32 AF XY: 0.632 AC XY: 46993 AN XY: 74352

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.604

Alfa AF: 0.605 Hom.: 3638

Bravo AF: 0.622

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.72

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: rs4924496; hg19: chr15-40995335;