ENST00000487861.5:c.1037-6124G>A

Variant names:

• chr14-68604882-G-A
• rs17829444
• ENST00000487861.5:c.1037-6124G>A

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-6124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,062 control chromosomes in the GnomAD database, including 2,434 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 0.17 (2434 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-6124G>A		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.*33+2179G>A		intron_variant	Intron 11 of 11		NP_001308738.1
RAD51B	NM_001321818.2	c.1037-78055G>A		intron_variant	Intron 10 of 10		NP_001308747.1
RAD51B	NM_001321815.1	c.923-6276G>A		intron_variant	Intron 9 of 9		NP_001308744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-6124G>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-45899G>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-78055G>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26184 AN: 151944 Hom.: 2432 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.172 AC: 26205 AN: 152062 Hom.: 2434 Cov.: 32 AF XY: 0.171 AC XY: 12725 AN XY: 74320

African (AFR) AF: 0.119 AC: 4931 AN: 41484

American (AMR) AF: 0.140 AC: 2145 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.143 AC: 738 AN: 5170

South Asian (SAS) AF: 0.101 AC: 488 AN: 4818

European-Finnish (FIN) AF: 0.246 AC: 2599 AN: 10552

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.208 AC: 14107 AN: 67976

Other (OTH) AF: 0.164 AC: 346 AN: 2110

Alfa AF: 0.191 Hom.: 11607

Bravo AF: 0.163

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.79
PhyloP100		0.14
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: rs17829444; hg19: chr14-69071599;