14-68322207-C-T

Variant names:

• chr14-68322207-C-T
• rs1956529
• NM_133510.4:c.853+30227C>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.853+30227C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,084 control chromosomes in the GnomAD database, including 21,295 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 0.49 (21295 hom., cov: 33)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 26 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.853+30227C>T		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+30227C>T		intron_variant	Intron 8 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74119 AN: 151966 Hom.: 21289 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.488 AC: 74143 AN: 152084 Hom.: 21295 Cov.: 33 AF XY: 0.490 AC XY: 36393 AN XY: 74318

African (AFR) AF: 0.167 AC: 6942 AN: 41490

American (AMR) AF: 0.583 AC: 8911 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1792 AN: 3464

East Asian (EAS) AF: 0.447 AC: 2314 AN: 5180

South Asian (SAS) AF: 0.651 AC: 3135 AN: 4818

European-Finnish (FIN) AF: 0.599 AC: 6323 AN: 10552

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43018 AN: 67986

Other (OTH) AF: 0.471 AC: 992 AN: 2108

Alfa AF: 0.572 Hom.: 53855

Bravo AF: 0.464

Asia WGS AF: 0.529 AC: 1841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.36
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: rs1956529; hg19: chr14-68788924;