rs961700

Positions:

• chr14-67864720-G-A
• chr14-67864720-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000471583.6(RAD51B):​c.316-283G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 522,082 control chromosomes in the GnomAD database, including 38,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13552 hom., cov: 32)
  • Exomes 𝑓: 0.35 (25002 hom.)
• Consequence: RAD51B ENST00000471583.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-67864720-G-A is Benign according to our data. Variant chr14-67864720-G-A is described in ClinVar as [Benign]. Clinvar id is 1183458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.316-283G>A		intron_variant		ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.316-283G>A		intron_variant		1	NM_133510.4	ENSP00000418859	P4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61668 AN: 151844 Hom.: 13526 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.0755

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.353 AC: 130794 AN: 370120 Hom.: 25002 AF XY: 0.347 AC XY: 71594 AN XY: 206064

Gnomad4 AFR exome AF: 0.558

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.446

Gnomad4 EAS exome AF: 0.0867

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.406 AC: 61738 AN: 151962 Hom.: 13552 Cov.: 32 AF XY: 0.397 AC XY: 29539 AN XY: 74316

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.0759

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.404

Alfa AF: 0.387 Hom.: 19700

Bravo AF: 0.411

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.81

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: rs961700; hg19: chr14-68331437;