rs4902623

Variant names:

• chr14-68644209-G-A
• rs4902623
• ENST00000488612.5:c.1037-6572G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68644209-G-A
• chr14-68644209-G-C
• chr14-68644209-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321818.2(RAD51B):​c.1037-38728G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,108 control chromosomes in the GnomAD database, including 29,364 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 (29364 hom., cov: 32)
• Consequence: RAD51B NM_001321818.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146
• Publications: 1 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

RAD51B-AS1 (HGNC:58171):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321818.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_001321818.2		c.1037-38728G>A		intron	N/A	NP_001308747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.1037-6572G>A		intron	N/A	ENSP00000420061.1
	RAD51B	ENST00000478014.5	TSL:3	n.384-38728G>A		intron	N/A
	RAD51B	ENST00000553595.5	TSL:3	n.614-38728G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93617 AN: 151990 Hom.: 29332 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.616 AC: 93698 AN: 152108 Hom.: 29364 Cov.: 32 AF XY: 0.623 AC XY: 46334 AN XY: 74386

African (AFR) AF: 0.613 AC: 25415 AN: 41482

American (AMR) AF: 0.694 AC: 10618 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3468

East Asian (EAS) AF: 0.952 AC: 4940 AN: 5190

South Asian (SAS) AF: 0.751 AC: 3626 AN: 4826

European-Finnish (FIN) AF: 0.619 AC: 6547 AN: 10578

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38407 AN: 67954

Other (OTH) AF: 0.622 AC: 1314 AN: 2112

Alfa AF: 0.581 Hom.: 21186

Bravo AF: 0.622

Asia WGS AF: 0.828 AC: 2879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4902623; hg19: chr14-69110926;