14-68595397-C-T

Variant names:

• chr14-68595397-C-T
• rs963918
• ENST00000487270.5:c.*794C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000487270.5(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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31490 hom., cov: 32)
  • Exomes 𝑓: 0.64 (185991 hom.)
• Consequence: RAD51B ENST00000487270.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 14-68595397-C-T is Benign according to our data. Variant chr14-68595397-C-T is described in ClinVar as Benign. ClinVar VariationId is 4077039.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
RAD51B	NM_133509.5	c.*794C>T		3_prime_UTR_variant	Exon 11 of 11		NP_598193.2
RAD51B	NM_001321821.2	c.1037-15609C>T		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.1037-7266C>T		intron_variant	Intron 10 of 11		NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.*794C>T		3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000419471.1
RAD51B	ENST00000487861.5	c.1037-15609C>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-55384C>T		intron_variant	Intron 10 of 11	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

African (AFR) AF: 0.662 AC: 13024 AN: 19676

American (AMR) AF: 0.566 AC: 1972 AN: 3486

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 5521 AN: 10274

East Asian (EAS) AF: 0.701 AC: 10538 AN: 15028

South Asian (SAS) AF: 0.650 AC: 11147 AN: 17154

European-Finnish (FIN) AF: 0.630 AC: 281 AN: 446

Middle Eastern (MID) AF: 0.572 AC: 1207 AN: 2110

European-Non Finnish (NFE) AF: 0.638 AC: 517820 AN: 811756

Other (OTH) AF: 0.633 AC: 21546 AN: 34064

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

African (AFR) AF: 0.674 AC: 27938 AN: 41464

American (AMR) AF: 0.595 AC: 9099 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1856 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3697 AN: 5176

South Asian (SAS) AF: 0.661 AC: 3189 AN: 4826

European-Finnish (FIN) AF: 0.620 AC: 6553 AN: 10566

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43226 AN: 67948

Other (OTH) AF: 0.628 AC: 1323 AN: 2108

Alfa AF: 0.631 Hom.: 50506

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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs963918; hg19: chr14-69062114;