rs6573824

Variant names:

• chr14-68272207-C-G
• rs6573824
• NM_133510.4:c.757-19677C>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.757-19677C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,216 control chromosomes in the GnomAD database, including 62,353 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 0.90 (62353 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.775
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-19677C>G		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.757-19677C>G		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136747 AN: 152096 Hom.: 62306 Cov.: 31

Gnomad AFR AF: 0.977

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.899 AC: 136842 AN: 152216 Hom.: 62353 Cov.: 31 AF XY: 0.891 AC XY: 66302 AN XY: 74412

African (AFR) AF: 0.977 AC: 40597 AN: 41548

American (AMR) AF: 0.750 AC: 11470 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2696 AN: 5154

South Asian (SAS) AF: 0.715 AC: 3438 AN: 4808

European-Finnish (FIN) AF: 0.923 AC: 9790 AN: 10604

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

European-Non Finnish (NFE) AF: 0.922 AC: 62718 AN: 68026

Other (OTH) AF: 0.891 AC: 1880 AN: 2110

Alfa AF: 0.903 Hom.: 34775

Bravo AF: 0.889

Asia WGS AF: 0.639 AC: 2221 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.28
PhyloP100		0.78
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: rs6573824; hg19: chr14-68738924;