14-68566513-G-T

Variant names:

• chr14-68566513-G-T
• rs7153476
• ENST00000487861.5:c.1037-44493G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487861.5(RAD51B):​c.1037-44493G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 151,972 control chromosomes in the GnomAD database, including 17,099 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 0.47 (17099 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-44493G>T		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1037-27972G>T		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321809.2	c.1037-36150G>T		intron_variant	Intron 10 of 11		NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-44493G>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-27972G>T		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-84268G>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70685 AN: 151854 Hom.: 17079 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.465 AC: 70742 AN: 151972 Hom.: 17099 Cov.: 32 AF XY: 0.459 AC XY: 34086 AN XY: 74276

African (AFR) AF: 0.553 AC: 22911 AN: 41428

American (AMR) AF: 0.392 AC: 5990 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3466

East Asian (EAS) AF: 0.119 AC: 616 AN: 5184

South Asian (SAS) AF: 0.441 AC: 2122 AN: 4812

European-Finnish (FIN) AF: 0.359 AC: 3783 AN: 10542

Middle Eastern (MID) AF: 0.548 AC: 159 AN: 290

European-Non Finnish (NFE) AF: 0.472 AC: 32046 AN: 67958

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

Alfa AF: 0.446 Hom.: 8406

Bravo AF: 0.467

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-0.29
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: rs7153476; hg19: chr14-69033230;