chr14-68301255-G-T

Variant names:

• chr14-68301255-G-T
• rs927220
• NM_133510.4:c.853+9275G>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+9275G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,936 control chromosomes in the GnomAD database, including 35,900 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 0.69 (35900 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453
• Publications: 10 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.735 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.853+9275G>T		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.853+9275G>T		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.853+9275G>T		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.853+9275G>T		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.853+9275G>T		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.853+9275G>T		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104005 AN: 151818 Hom.: 35867 Cov.: 31

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.685 AC: 104081 AN: 151936 Hom.: 35900 Cov.: 31 AF XY: 0.682 AC XY: 50659 AN XY: 74252

African (AFR) AF: 0.611 AC: 25326 AN: 41436

American (AMR) AF: 0.746 AC: 11383 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2152 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3050 AN: 5158

South Asian (SAS) AF: 0.679 AC: 3263 AN: 4806

European-Finnish (FIN) AF: 0.691 AC: 7290 AN: 10544

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.726 AC: 49360 AN: 67954

Other (OTH) AF: 0.659 AC: 1394 AN: 2114

Alfa AF: 0.708 Hom.: 76894

Bravo AF: 0.683

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.23
PhyloP100		0.45
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: rs927220; hg19: chr14-68767972;