14-67835050-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_133510.4(RAD51B):c.199-22dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,528,220 control chromosomes in the GnomAD database, including 89,705 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11283 hom., cov: 0)
  • Exomes 𝑓: 0.34 (78422 hom.)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.233

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.

• BP6: Variant 14-67835050-G-GA is Benign according to our data. Variant chr14-67835050-G-GA is described in ClinVar as [Benign]. Clinvar id is 1270868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.199-22dup		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.199-22dup		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56473 AN: 151596 Hom.: 11256 Cov.: 0

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.306 AC: 73641 AN: 240828 Hom.: 11963 AF XY: 0.305 AC XY: 39707 AN XY: 130310

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.230

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.336 AC: 462458 AN: 1376506 Hom.: 78422 Cov.: 25 AF XY: 0.333 AC XY: 229492 AN XY: 688984

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.373 AC: 56541 AN: 151714 Hom.: 11283 Cov.: 0 AF XY: 0.364 AC XY: 26965 AN XY: 74122

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.374

Bravo AF: 0.376

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34564590; hg19: chr14-68301767;