ENST00000487861.5:c.1037-11412C>A

Variant names:

• chr14-68599594-C-A
• rs2064827
• ENST00000487861.5:c.1037-11412C>A

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-11412C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,102 control chromosomes in the GnomAD database, including 41,054 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 0.73 (41054 hom., cov: 31)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-11412C>A		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.1037-3069C>A		intron_variant	Intron 10 of 11		NP_001308738.1
RAD51B	NM_001321810.2	c.1037-3069C>A		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.1037-11412C>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-51187C>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-83343C>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110800 AN: 151984 Hom.: 41055 Cov.: 31

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.729 AC: 110832 AN: 152102 Hom.: 41054 Cov.: 31 AF XY: 0.732 AC XY: 54424 AN XY: 74378

African (AFR) AF: 0.614 AC: 25460 AN: 41462

American (AMR) AF: 0.684 AC: 10456 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2429 AN: 3470

East Asian (EAS) AF: 0.736 AC: 3808 AN: 5174

South Asian (SAS) AF: 0.745 AC: 3587 AN: 4814

European-Finnish (FIN) AF: 0.854 AC: 9056 AN: 10600

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.787 AC: 53521 AN: 67978

Other (OTH) AF: 0.727 AC: 1537 AN: 2114

Alfa AF: 0.762 Hom.: 185631

Bravo AF: 0.708

Asia WGS AF: 0.741 AC: 2577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.70
DANN	Benign	0.64
PhyloP100		-0.062
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: rs2064827; hg19: chr14-69066311;