chr14-68318360-G-A

Variant names:

• chr14-68318360-G-A
• rs8017304
• NM_133510.4:c.853+26380G>A

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+26380G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,914 control chromosomes in the GnomAD database, including 23,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.54 (23484 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.385
• Publications: 58 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 (SAS) allele frequency at 95% confidence interval = 0.631 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.853+26380G>A		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.853+26380G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.853+26380G>A		intron	N/A	NP_598193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.853+26380G>A		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.853+26380G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.853+26380G>A		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82082 AN: 151796 Hom.: 23469 Cov.: 31

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.541 AC: 82130 AN: 151914 Hom.: 23484 Cov.: 31 AF XY: 0.541 AC XY: 40157 AN XY: 74228

African (AFR) AF: 0.350 AC: 14484 AN: 41402

American (AMR) AF: 0.606 AC: 9245 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2312 AN: 5168

South Asian (SAS) AF: 0.650 AC: 3135 AN: 4824

European-Finnish (FIN) AF: 0.599 AC: 6302 AN: 10520

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43051 AN: 67966

Other (OTH) AF: 0.517 AC: 1088 AN: 2106

Alfa AF: 0.606 Hom.: 82045

Bravo AF: 0.525

Asia WGS AF: 0.541 AC: 1884 AN: 3476

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

Department of Ophthalmology and Visual Sciences Kyoto University

Significance: not provided

Review Status: no classification provided

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.59
DANN	Benign	0.29
PhyloP100		-0.39
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: rs8017304; hg19: chr14-68785077;