14-68595397-C-T

Position:

• chr14-68595397-C-T

Variant summary

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

The NM_133509.5(RAD51B):​c.*794C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,066,042 control chromosomes in the GnomAD database, including 217,481 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 0.64 (31490 hom., cov: 32)
  • Exomes 𝑓: 0.64 (185991 hom.)
• Consequence: RAD51B NM_133509.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133509.5	c.*794C>T		3_prime_UTR_variant	11/11		NP_598193.2
RAD51B	NM_001321821.2	c.1037-15609C>T		intron_variant			NP_001308750.1
RAD51B	NM_001321809.2	c.1037-7266C>T		intron_variant			NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.*794C>T		3_prime_UTR_variant	11/11	1		ENSP00000419471.1
RAD51B	ENST00000487861.5	c.1037-15609C>T		intron_variant		1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-55384C>T		intron_variant		1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97688 AN: 151930 Hom.: 31467 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.638 AC: 583056 AN: 913994 Hom.: 185991 Cov.: 34 AF XY: 0.637 AC XY: 268956 AN XY: 421904

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.537

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.650

Gnomad4 FIN exome AF: 0.630

Gnomad4 NFE exome AF: 0.638

Gnomad4 OTH exome AF: 0.633

GnomAD4 genome AF: 0.643 AC: 97759 AN: 152048 Hom.: 31490 Cov.: 32 AF XY: 0.644 AC XY: 47848 AN XY: 74314

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.628

Alfa AF: 0.629 Hom.: 40299

Bravo AF: 0.640

Asia WGS AF: 0.702 AC: 2441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs963918; hg19: chr14-69062114;