NM_133510.4:c.958-28123C>T

Variant names:

• chr14-68440049-C-T
• rs2331703
• NM_133510.4:c.958-28123C>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.958-28123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,258 control chromosomes in the GnomAD database, including 55,397 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 0.85 (55397 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.521
• 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=-0.74).
• 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.958-28123C>T		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.958-28123C>T		intron_variant	Intron 9 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129416 AN: 152140 Hom.: 55329 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.851 AC: 129546 AN: 152258 Hom.: 55397 Cov.: 32 AF XY: 0.850 AC XY: 63307 AN XY: 74438

African (AFR) AF: 0.935 AC: 38841 AN: 41554

American (AMR) AF: 0.847 AC: 12960 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2533 AN: 3472

East Asian (EAS) AF: 0.968 AC: 5018 AN: 5182

South Asian (SAS) AF: 0.805 AC: 3881 AN: 4820

European-Finnish (FIN) AF: 0.827 AC: 8768 AN: 10596

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54904 AN: 68016

Other (OTH) AF: 0.810 AC: 1712 AN: 2114

Alfa AF: 0.846 Hom.: 19483

Bravo AF: 0.855

Asia WGS AF: 0.897 AC: 3120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.1
DANN	Benign	0.73
PhyloP100		-0.52
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: rs2331703; hg19: chr14-68906766;