rs11626138

Variant names:

• chr14-68320276-A-G
• rs11626138
• NM_133510.4:c.853+28296A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-68320276-A-G
• chr14-68320276-A-T

Variant summary

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

The NM_133510.4(RAD51B):​c.853+28296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,196 control chromosomes in the GnomAD database, including 21,306 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 0.49 (21306 hom., cov: 33)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.853+28296A>G		intron_variant	Intron 8 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.853+28296A>G		intron_variant	Intron 8 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74147 AN: 152078 Hom.: 21300 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.487 AC: 74171 AN: 152196 Hom.: 21306 Cov.: 33 AF XY: 0.489 AC XY: 36415 AN XY: 74404

African (AFR) AF: 0.167 AC: 6943 AN: 41522

American (AMR) AF: 0.583 AC: 8911 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2311 AN: 5174

South Asian (SAS) AF: 0.650 AC: 3139 AN: 4828

European-Finnish (FIN) AF: 0.598 AC: 6344 AN: 10600

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43021 AN: 67998

Other (OTH) AF: 0.470 AC: 994 AN: 2116

Alfa AF: 0.534 Hom.: 3109

Bravo AF: 0.464

Asia WGS AF: 0.529 AC: 1841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	16
DANN	Benign	0.47
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11626138; hg19: chr14-68786993;