14-68341681-T-C

Variant names:

• chr14-68341681-T-C
• rs6573834
• NM_133510.4:c.853+49701T>C

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+49701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,128 control chromosomes in the GnomAD database, including 53,823 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 0.84 (53823 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716
• Publications: 15 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 = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.853+49701T>C		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+49701T>C		intron_variant	Intron 8 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127512 AN: 152010 Hom.: 53763 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.839 AC: 127630 AN: 152128 Hom.: 53823 Cov.: 31 AF XY: 0.838 AC XY: 62281 AN XY: 74362

African (AFR) AF: 0.903 AC: 37492 AN: 41500

American (AMR) AF: 0.840 AC: 12839 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2479 AN: 3468

East Asian (EAS) AF: 0.991 AC: 5134 AN: 5182

South Asian (SAS) AF: 0.844 AC: 4067 AN: 4816

European-Finnish (FIN) AF: 0.780 AC: 8238 AN: 10562

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.805 AC: 54742 AN: 67996

Other (OTH) AF: 0.807 AC: 1705 AN: 2112

Alfa AF: 0.814 Hom.: 202384

Bravo AF: 0.845

Asia WGS AF: 0.892 AC: 3103 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	1.8
DANN	Benign	0.41
PhyloP100		-0.72
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: rs6573834; hg19: chr14-68808398;