rs17756147

Positions:

• chr14-68569410-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000487861.5(RAD51B):​c.1037-41596G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,196 control chromosomes in the GnomAD database, including 2,509 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 (2509 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.98

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_001321809.2	c.1037-33253G>A		intron_variant			NP_001308738.1
RAD51B	NM_001321810.2	c.1037-33253G>A		intron_variant			NP_001308739.1
RAD51B	NM_001321815.1	c.923-41748G>A		intron_variant			NP_001308744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.1037-25075G>A		intron_variant		1		ENSP00000419471
RAD51B	ENST00000487861.5	c.1037-41596G>A		intron_variant		1		ENSP00000419881
RAD51B	ENST00000488612.5	c.1037-81371G>A		intron_variant		1		ENSP00000420061

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24189 AN: 152078 Hom.: 2510 Cov.: 32

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.159 AC: 24205 AN: 152196 Hom.: 2509 Cov.: 32 AF XY: 0.157 AC XY: 11683 AN XY: 74412

Gnomad4 AFR AF: 0.0461

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.152

Alfa AF: 0.207 Hom.: 858

Bravo AF: 0.150

Asia WGS AF: 0.0540 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17756147; hg19: chr14-69036127;