rs8008961

Positions:

• chr14-68285926-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471583.6(RAD51B):​c.757-5958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,066 control chromosomes in the GnomAD database, including 6,817 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 0.29 (6817 hom., cov: 32)
• Consequence: RAD51B ENST00000471583.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-5958C>T		intron_variant		ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-5958C>T		intron_variant		1	NM_133510.4	ENSP00000418859	P4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43971 AN: 151948 Hom.: 6812 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.289 AC: 43996 AN: 152066 Hom.: 6817 Cov.: 32 AF XY: 0.287 AC XY: 21359 AN XY: 74328

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.00887

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.315

Alfa AF: 0.275 Hom.: 1025

Bravo AF: 0.289

Asia WGS AF: 0.136 AC: 471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs8008961; hg19: chr14-68752643;