ENST00000488612.5:c.1037-31785G>A

Variant names:

• chr14-68618996-G-A
• rs2331780
• ENST00000488612.5:c.1037-31785G>A

Variant summary

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

The ENST00000488612.5(RAD51B):​c.1037-31785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,148 control chromosomes in the GnomAD database, including 2,438 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 0.16 (2438 hom., cov: 32)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 5 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

ENSG00000306917 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321818.2	c.1037-63941G>A		intron_variant	Intron 10 of 10		NP_001308747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.1037-31785G>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-63941G>A		intron_variant	Intron 4 of 4	3
RAD51B	ENST00000553595.5	n.614-63941G>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24818 AN: 152032 Hom.: 2439 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.163 AC: 24813 AN: 152148 Hom.: 2438 Cov.: 32 AF XY: 0.167 AC XY: 12418 AN XY: 74364

African (AFR) AF: 0.0536 AC: 2227 AN: 41530

American (AMR) AF: 0.209 AC: 3196 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 859 AN: 3472

East Asian (EAS) AF: 0.121 AC: 628 AN: 5178

South Asian (SAS) AF: 0.236 AC: 1136 AN: 4816

European-Finnish (FIN) AF: 0.229 AC: 2413 AN: 10548

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13783 AN: 68004

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.185 Hom.: 6439

Bravo AF: 0.155

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.71
PhyloP100		-0.24
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: rs2331780; hg19: chr14-69085713;