rs8013316

Variant names:

• chr14-68724947-A-C
• rs8013316
• ENST00000488612.5:c.*12-4861A>C

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*12-4861A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,144 control chromosomes in the GnomAD database, including 430 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 0.062 (430 hom., cov: 30)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.582
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.*12-4861A>C		intron_variant	Intron 11 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9431 AN: 152026 Hom.: 432 Cov.: 30

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0663

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0619 AC: 9424 AN: 152144 Hom.: 430 Cov.: 30 AF XY: 0.0677 AC XY: 5032 AN XY: 74368

African (AFR) AF: 0.0180 AC: 748 AN: 41578

American (AMR) AF: 0.0447 AC: 684 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3466

East Asian (EAS) AF: 0.179 AC: 919 AN: 5134

South Asian (SAS) AF: 0.132 AC: 636 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1651 AN: 10570

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0663 AC: 4504 AN: 67960

Other (OTH) AF: 0.0530 AC: 112 AN: 2114

Alfa AF: 0.0617 Hom.: 50

Bravo AF: 0.0505

Asia WGS AF: 0.156 AC: 544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.23
PhyloP100		-0.58
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: rs8013316; hg19: chr14-69191664;