rs2331704

Variant names:

• chr14-68440116-G-A
• rs2331704
• NM_133510.4:c.958-28056G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68440116-G-A
• chr14-68440116-G-C
• chr14-68440116-G-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.958-28056G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 152,242 control chromosomes in the GnomAD database, including 54,323 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 0.84 (54323 hom., cov: 33)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133510.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.958-28056G>A		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.958-28056G>A		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.958-28056G>A		intron	N/A	NP_598193.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.958-28056G>A		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.958-28056G>A		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.958-28056G>A		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128258 AN: 152122 Hom.: 54258 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.844

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: 0.804

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

GnomAD4 genome AF: 0.843 AC: 128386 AN: 152242 Hom.: 54323 Cov.: 33 AF XY: 0.843 AC XY: 62752 AN XY: 74432

African (AFR) AF: 0.909 AC: 37743 AN: 41532

American (AMR) AF: 0.844 AC: 12910 AN: 15298

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

East Asian (EAS) AF: 0.968 AC: 5016 AN: 5180

South Asian (SAS) AF: 0.805 AC: 3883 AN: 4826

European-Finnish (FIN) AF: 0.827 AC: 8765 AN: 10596

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

European-Non Finnish (NFE) AF: 0.807 AC: 54903 AN: 68018

Other (OTH) AF: 0.806 AC: 1704 AN: 2114

Alfa AF: 0.812 Hom.: 29823

Bravo AF: 0.847

Asia WGS AF: 0.894 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		-0.13
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: rs2331704; hg19: chr14-68906833;