rs2842320

Variant names:

• chr14-68477356-A-G
• rs2842320
• NM_133510.4:c.1037-292A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_133510.4(RAD51B):​c.1037-292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,172 control chromosomes in the GnomAD database, including 1,966 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1966 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 14-68477356-A-G is Benign according to our data. Variant chr14-68477356-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.1037-292A>G		intron_variant	Intron 10 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.1037-292A>G		intron_variant	Intron 10 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22797 AN: 152054 Hom.: 1967 Cov.: 32

Gnomad AFR AF: 0.0761

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.150 AC: 22786 AN: 152172 Hom.: 1966 Cov.: 32 AF XY: 0.149 AC XY: 11094 AN XY: 74390

African (AFR) AF: 0.0759 AC: 3152 AN: 41516

American (AMR) AF: 0.160 AC: 2453 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3472

East Asian (EAS) AF: 0.0300 AC: 155 AN: 5174

South Asian (SAS) AF: 0.144 AC: 694 AN: 4814

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10598

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13039 AN: 67986

Other (OTH) AF: 0.198 AC: 418 AN: 2110

Alfa AF: 0.182 Hom.: 1431

Bravo AF: 0.148

Asia WGS AF: 0.0880 AC: 305 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.12
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: rs2842320; hg19: chr14-68944073;