rs765899

Positions:

• chr14-68497029-C-T

Variant summary

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

The NM_001321821.2(RAD51B):​c.1036+28779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,199,680 control chromosomes in the GnomAD database, including 94,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (9737 hom., cov: 32)
  • Exomes 𝑓: 0.40 (85134 hom.)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.694

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 14-68497029-C-T is Benign according to our data. Variant chr14-68497029-C-T is described in ClinVar as [Benign]. Clinvar id is 1247355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1036+28779C>T		intron_variant			NP_001308750.1
RAD51B	NM_133509.5	c.1036+28779C>T		intron_variant			NP_598193.2
RAD51B	NM_001321812.1	c.1036+28779C>T		intron_variant			NP_001308741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1036+28779C>T		intron_variant		1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+28779C>T		intron_variant		1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+28779C>T		intron_variant		1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50614 AN: 152018 Hom.: 9728 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.396 AC: 414788 AN: 1047544 Hom.: 85134 AF XY: 0.402 AC XY: 207264 AN XY: 515038

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.541

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.387

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.333 AC: 50631 AN: 152136 Hom.: 9737 Cov.: 32 AF XY: 0.338 AC XY: 25116 AN XY: 74354

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.343

Alfa AF: 0.392 Hom.: 24173

Bravo AF: 0.326

Asia WGS AF: 0.480 AC: 1671 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 14, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs765899; hg19: chr14-68963746; COSMIC: COSV66845116;