rs382179

Variant names:

• chr14-68713112-T-C
• rs382179
• ENST00000488612.5:c.*12-16696T>C

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*12-16696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,026 control chromosomes in the GnomAD database, including 29,007 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 0.61 (29007 hom., cov: 31)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.714 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.*12-16696T>C		intron_variant	Intron 11 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92693 AN: 151908 Hom.: 28985 Cov.: 31

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.610 AC: 92759 AN: 152026 Hom.: 29007 Cov.: 31 AF XY: 0.612 AC XY: 45452 AN XY: 74312

African (AFR) AF: 0.494 AC: 20493 AN: 41444

American (AMR) AF: 0.583 AC: 8914 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2386 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2029 AN: 5172

South Asian (SAS) AF: 0.734 AC: 3542 AN: 4824

European-Finnish (FIN) AF: 0.706 AC: 7452 AN: 10560

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45919 AN: 67962

Other (OTH) AF: 0.600 AC: 1264 AN: 2108

Alfa AF: 0.661 Hom.: 114460

Bravo AF: 0.593

Asia WGS AF: 0.600 AC: 2089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.37
PhyloP100		0.21
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: rs382179; hg19: chr14-69179829;