rs766897041

Variant names:

• chr14-67825494-A-C
• rs766897041
• NM_133510.4:c.115A>C

Your query was ambiguous. Multiple possible variants found:

• chr14-67825494-A-C
• chr14-67825494-A-G
• chr14-67825494-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321817.2(RAD51B):​c.-341A>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000205 in 1,461,348 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RAD51B NM_001321817.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22664565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.115A>C	p.Met39Leu	missense_variant	Exon 3 of 11	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.115A>C	p.Met39Leu	missense_variant	Exon 3 of 11	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461348 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.036	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.022	T;.;T;T;.;.;.
Eigen	Benign	-0.18
Eigen_PC	Benign	0.045
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T;T;T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	.;M;M;.;M;.;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.96	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.52	T;T;T;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;T;T;T
Polyphen		0.54	P;B;B;.;B;.;.
Vest4		0.52
MutPred		0.44		Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);Gain of catalytic residue at S34 (P = 0.0054);
MVP		0.54
MPC		0.20
ClinPred		0.43	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs766897041; hg19: chr14-68292211;