chr15-40729082-C-G

Variant names:

• chr15-40729082-C-G
• rs4417527
• NM_002875.5:c.644+258C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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 -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 VariationId 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.

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.644+258C>G		intron	N/A	NP_002866.2
	RAD51	NM_001164269.2		c.647+258C>G		intron	N/A	NP_001157741.1	Q06609-4
	RAD51	NM_133487.4		c.647+258C>G		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.644+258C>G		intron	N/A	ENSP00000267868.3	Q06609-1
	RAD51	ENST00000532743.6	TSL:2	c.644+258C>G		intron	N/A	ENSP00000433924.2	Q06609-1
	RAD51	ENST00000423169.6	TSL:1	c.644+258C>G		intron	N/A	ENSP00000406602.2	Q06609-3

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

African (AFR) AF: 0.242 AC: 10023 AN: 41434

American (AMR) AF: 0.350 AC: 5341 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 713 AN: 3468

East Asian (EAS) AF: 0.671 AC: 3465 AN: 5162

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4810

European-Finnish (FIN) AF: 0.154 AC: 1624 AN: 10560

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10432 AN: 67924

Other (OTH) AF: 0.226 AC: 477 AN: 2110

Alfa AF: 0.179 Hom.: 358

Bravo AF: 0.246

Asia WGS AF: 0.461 AC: 1604 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		-0.12
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: rs4417527; hg19: chr15-41021280;