rs916962

Variant names:

• chr14-68526861-G-A
• rs916962
• ENST00000487861.5:c.1036+58611G>A

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1036+58611G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,182 control chromosomes in the GnomAD database, including 3,615 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 0.20 (3615 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 4 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

LOC124903334 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903334	XR_007064222.1	n.10570C>T		non_coding_transcript_exon_variant	Exon 2 of 2
LOC124903334	XR_007064223.1	n.10570C>T		non_coding_transcript_exon_variant	Exon 2 of 3
RAD51B	NM_001321821.2	c.1036+58611G>A		intron_variant	Intron 10 of 10		NP_001308750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+58611G>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+58611G>A		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+58611G>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30097 AN: 152062 Hom.: 3618 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.198 AC: 30099 AN: 152182 Hom.: 3615 Cov.: 32 AF XY: 0.206 AC XY: 15363 AN XY: 74400

African (AFR) AF: 0.0611 AC: 2537 AN: 41544

American (AMR) AF: 0.261 AC: 3993 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1044 AN: 5166

South Asian (SAS) AF: 0.300 AC: 1448 AN: 4820

European-Finnish (FIN) AF: 0.357 AC: 3778 AN: 10588

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15850 AN: 67984

Other (OTH) AF: 0.194 AC: 410 AN: 2110

Alfa AF: 0.227 Hom.: 3483

Bravo AF: 0.181

Asia WGS AF: 0.263 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		1.4
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: rs916962; hg19: chr14-68993578;