ENST00000487861.5:c.1037-9339A>G

Variant names:

• chr14-68601667-A-G
• rs12878344
• ENST00000487861.5:c.1037-9339A>G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-9339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 151,890 control chromosomes in the GnomAD database, including 35,320 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 0.68 (35320 hom., cov: 30)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-9339A>G		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.1037-996A>G		intron_variant	Intron 10 of 11		NP_001308738.1
RAD51B	NM_001321810.2	c.1037-996A>G		intron_variant	Intron 10 of 10		NP_001308739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-9339A>G		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-49114A>G		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-81270A>G		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 102978 AN: 151772 Hom.: 35307 Cov.: 30

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.678 AC: 103033 AN: 151890 Hom.: 35320 Cov.: 30 AF XY: 0.679 AC XY: 50395 AN XY: 74246

African (AFR) AF: 0.645 AC: 26664 AN: 41370

American (AMR) AF: 0.625 AC: 9544 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3466

East Asian (EAS) AF: 0.740 AC: 3828 AN: 5170

South Asian (SAS) AF: 0.522 AC: 2518 AN: 4820

European-Finnish (FIN) AF: 0.806 AC: 8526 AN: 10574

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.704 AC: 47844 AN: 67918

Other (OTH) AF: 0.662 AC: 1393 AN: 2104

Alfa AF: 0.682 Hom.: 72208

Bravo AF: 0.664

Asia WGS AF: 0.647 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.48
PhyloP100		0.0040
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: rs12878344; hg19: chr14-69068384;