chr14-68261762-T-C

Variant names:

• chr14-68261762-T-C
• rs17105278
• NM_133510.4:c.757-30122T>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.757-30122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,206 control chromosomes in the GnomAD database, including 10,502 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 0.35 (10502 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 13 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-30122T>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.757-30122T>C		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52925 AN: 151088 Hom.: 10483 Cov.: 31

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.350 AC: 52981 AN: 151206 Hom.: 10502 Cov.: 31 AF XY: 0.346 AC XY: 25606 AN XY: 73966

African (AFR) AF: 0.528 AC: 21809 AN: 41330

American (AMR) AF: 0.269 AC: 4099 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3468

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5182

South Asian (SAS) AF: 0.205 AC: 985 AN: 4814

European-Finnish (FIN) AF: 0.311 AC: 3266 AN: 10514

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 19928 AN: 67380

Other (OTH) AF: 0.370 AC: 777 AN: 2100

Alfa AF: 0.331 Hom.: 1235

Bravo AF: 0.358

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.9
DANN	Benign	0.70
PhyloP100		0.15
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: rs17105278; hg19: chr14-68728479; COSMIC: COSV66855830;