NM_133510.4:c.756+8310T>C

Variant names:

• chr14-67895514-T-C
• rs1015023
• NM_133510.4:c.756+8310T>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.756+8310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,022 control chromosomes in the GnomAD database, including 14,406 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 0.42 (14406 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.756+8310T>C		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.756+8310T>C		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63282 AN: 151904 Hom.: 14368 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.417 AC: 63363 AN: 152022 Hom.: 14406 Cov.: 31 AF XY: 0.408 AC XY: 30294 AN XY: 74312

African (AFR) AF: 0.576 AC: 23885 AN: 41452

American (AMR) AF: 0.320 AC: 4884 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3464

East Asian (EAS) AF: 0.0746 AC: 387 AN: 5188

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4816

European-Finnish (FIN) AF: 0.311 AC: 3291 AN: 10570

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26748 AN: 67942

Other (OTH) AF: 0.410 AC: 865 AN: 2112

Alfa AF: 0.392 Hom.: 6192

Bravo AF: 0.423

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		-0.11
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: rs1015023; hg19: chr14-68362231;