chr15-40703137-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

RAD51 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group R

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• mirror movements 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	NM_002875.5	MANE Select	c.225+1936T>C		intron	N/A	NP_002866.2
	RAD51	NM_001164269.2		c.346+1211T>C		intron	N/A	NP_001157741.1	Q06609-4
	RAD51	NM_133487.4		c.346+1211T>C		intron	N/A	NP_597994.3	Q06609-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	ENST00000267868.8	TSL:1 MANE Select	c.225+1936T>C		intron	N/A	ENSP00000267868.3	Q06609-1
	RAD51	ENST00000532743.6	TSL:2	c.225+1936T>C		intron	N/A	ENSP00000433924.2	Q06609-1
	RAD51	ENST00000423169.6	TSL:1	c.225+1936T>C		intron	N/A	ENSP00000406602.2	Q06609-3

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

African (AFR) AF: 0.598 AC: 24799 AN: 41488

American (AMR) AF: 0.679 AC: 10365 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3468

East Asian (EAS) AF: 0.926 AC: 4800 AN: 5184

South Asian (SAS) AF: 0.773 AC: 3733 AN: 4828

European-Finnish (FIN) AF: 0.693 AC: 7323 AN: 10564

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39349 AN: 67984

Other (OTH) AF: 0.604 AC: 1277 AN: 2114

Alfa AF: 0.622 Hom.: 8903

Bravo AF: 0.622

Asia WGS AF: 0.841 AC: 2924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.72
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4924496; hg19: chr15-40995335;