rs4902610

Variant names:

• chr14-68607109-C-T
• rs4902610
• ENST00000487861.5:c.1037-3897C>T

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-3897C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,092 control chromosomes in the GnomAD database, including 5,052 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 0.24 (5052 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 3 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

ENSG00000287385 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487861.5. 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_001321821.2		c.1037-3897C>T		intron	N/A	NP_001308750.1
	RAD51B	NM_001321809.2		c.*34-3897C>T		intron	N/A	NP_001308738.1
	RAD51B	NM_001321818.2		c.1037-75828C>T		intron	N/A	NP_001308747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-3897C>T		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-43672C>T		intron	N/A	ENSP00000420061.1
	RAD51B	ENST00000478014.5	TSL:3	n.384-75828C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37184 AN: 151974 Hom.: 5036 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.245 AC: 37241 AN: 152092 Hom.: 5052 Cov.: 32 AF XY: 0.251 AC XY: 18695 AN XY: 74370

African (AFR) AF: 0.222 AC: 9198 AN: 41476

American (AMR) AF: 0.312 AC: 4772 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 617 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3124 AN: 5168

South Asian (SAS) AF: 0.288 AC: 1389 AN: 4816

European-Finnish (FIN) AF: 0.275 AC: 2904 AN: 10576

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14527 AN: 67990

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.228 Hom.: 6726

Bravo AF: 0.252

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.16
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: rs4902610; hg19: chr14-69073826;