rs963917

Positions:

• chr14-68595606-G-A
• chr14-68595606-G-C

Variant summary

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

The NM_133509.5(RAD51B):​c.*1003G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,064,476 control chromosomes in the GnomAD database, including 50,393 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 0.27 (6112 hom., cov: 32)
  • Exomes 𝑓: 0.31 (44281 hom.)
• Consequence: RAD51B NM_133509.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133509.5	c.*1003G>A		3_prime_UTR_variant	11/11		NP_598193.2
RAD51B	NM_001321821.2	c.1037-15400G>A		intron_variant			NP_001308750.1
RAD51B	NM_001321809.2	c.1037-7057G>A		intron_variant			NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.*1003G>A		3_prime_UTR_variant	11/11	1		ENSP00000419471.1
RAD51B	ENST00000487861.5	c.1037-15400G>A		intron_variant		1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-55175G>A		intron_variant		1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40572 AN: 151944 Hom.: 6113 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.308 AC: 280858 AN: 912414 Hom.: 44281 Cov.: 32 AF XY: 0.308 AC XY: 129656 AN XY: 421220

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.488

Gnomad4 SAS exome AF: 0.343

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.267 AC: 40572 AN: 152062 Hom.: 6112 Cov.: 32 AF XY: 0.273 AC XY: 20273 AN XY: 74326

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.273

Alfa AF: 0.298 Hom.: 13251

Bravo AF: 0.257

Asia WGS AF: 0.411 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs963917; hg19: chr14-69062323; COSMIC: COSV66848203; COSMIC: COSV66848203;