14-68446468-A-G

Variant names:

• chr14-68446468-A-G
• rs2753403
• NM_133510.4:c.958-21704A>G

Variant summary

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

The NM_133510.4(RAD51B):​c.958-21704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,022 control chromosomes in the GnomAD database, including 47,867 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 0.79 (47867 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• 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

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 (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.958-21704A>G		intron_variant	Intron 9 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.958-21704A>G		intron_variant	Intron 9 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120303 AN: 151904 Hom.: 47831 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.792 AC: 120395 AN: 152022 Hom.: 47867 Cov.: 31 AF XY: 0.794 AC XY: 58976 AN XY: 74298

African (AFR) AF: 0.727 AC: 30126 AN: 41412

American (AMR) AF: 0.820 AC: 12540 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2539 AN: 3470

East Asian (EAS) AF: 0.968 AC: 5009 AN: 5172

South Asian (SAS) AF: 0.850 AC: 4103 AN: 4826

European-Finnish (FIN) AF: 0.827 AC: 8722 AN: 10544

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54858 AN: 67996

Other (OTH) AF: 0.758 AC: 1597 AN: 2108

Alfa AF: 0.806 Hom.: 23716

Bravo AF: 0.788

Asia WGS AF: 0.894 AC: 3110 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	6.8
DANN	Benign	0.38
PhyloP100		-1.9
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: rs2753403; hg19: chr14-68913185;