rs12588940

Variant names:

• chr14-68565151-T-A
• rs12588940
• ENST00000487861.5:c.1037-45855T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68565151-T-A
• chr14-68565151-T-C
• chr14-68565151-T-G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-45855T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,052 control chromosomes in the GnomAD database, including 5,034 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 0.25 (5034 hom., cov: 33)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 3 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

ENSG00000306173 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903335	XR_007064224.1	n.100A>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903335	XR_007064225.1	n.100A>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 3
LOC124903335	XR_007064226.1	n.100A>T		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-45855T>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-29334T>A		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-85630T>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38674 AN: 151934 Hom.: 5012 Cov.: 33

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.255 AC: 38735 AN: 152052 Hom.: 5034 Cov.: 33 AF XY: 0.254 AC XY: 18861 AN XY: 74318

African (AFR) AF: 0.243 AC: 10076 AN: 41482

American (AMR) AF: 0.250 AC: 3828 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3470

East Asian (EAS) AF: 0.409 AC: 2109 AN: 5156

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2380 AN: 10578

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17406 AN: 67948

Other (OTH) AF: 0.269 AC: 566 AN: 2108

Alfa AF: 0.257 Hom.: 643

Bravo AF: 0.259

Asia WGS AF: 0.336 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.074
DANN	Benign	0.70
PhyloP100		-2.1
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: rs12588940; hg19: chr14-69031868;