rs1957572

Variant names:

• chr14-68269754-C-T
• rs1957572
• NM_133510.4:c.757-22130C>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.757-22130C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,312 control chromosomes in the GnomAD database, including 63,418 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 0.91 (63418 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176
• Publications: 10 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-22130C>T		intron_variant	Intron 7 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-22130C>T		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138242 AN: 152192 Hom.: 63369 Cov.: 32

Gnomad AFR AF: 0.979

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.806

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.924

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.905

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

GnomAD4 genome AF: 0.908 AC: 138348 AN: 152312 Hom.: 63418 Cov.: 32 AF XY: 0.901 AC XY: 67082 AN XY: 74478

African (AFR) AF: 0.979 AC: 40718 AN: 41576

American (AMR) AF: 0.805 AC: 12317 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 3117 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3167 AN: 5174

South Asian (SAS) AF: 0.717 AC: 3462 AN: 4826

European-Finnish (FIN) AF: 0.924 AC: 9804 AN: 10612

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62716 AN: 68036

Other (OTH) AF: 0.905 AC: 1915 AN: 2116

Alfa AF: 0.910 Hom.: 164391

Bravo AF: 0.905

Asia WGS AF: 0.678 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.66
PhyloP100		-0.18
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: rs1957572; hg19: chr14-68736471;