rs8008961

Variant names:

• chr14-68285926-C-T
• rs8008961
• NM_133510.4:c.757-5958C>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.757-5958C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,066 control chromosomes in the GnomAD database, including 6,817 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 0.29 (6817 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 22 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 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.757-5958C>T		intron	N/A	NP_598194.1	O15315-2
	RAD51B	NM_001321821.2		c.757-5958C>T		intron	N/A	NP_001308750.1	C9JYJ0
	RAD51B	NM_133509.5		c.757-5958C>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.757-5958C>T		intron	N/A	ENSP00000418859.1	O15315-2
	RAD51B	ENST00000487861.5	TSL:1	c.757-5958C>T		intron	N/A	ENSP00000419881.1	C9JYJ0
	RAD51B	ENST00000487270.5	TSL:1	c.757-5958C>T		intron	N/A	ENSP00000419471.1	O15315-3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43971 AN: 151948 Hom.: 6812 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.00885

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.289 AC: 43996 AN: 152066 Hom.: 6817 Cov.: 32 AF XY: 0.287 AC XY: 21359 AN XY: 74328

African (AFR) AF: 0.344 AC: 14248 AN: 41438

American (AMR) AF: 0.241 AC: 3679 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1312 AN: 3472

East Asian (EAS) AF: 0.00887 AC: 46 AN: 5188

South Asian (SAS) AF: 0.187 AC: 901 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3257 AN: 10572

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19467 AN: 67972

Other (OTH) AF: 0.315 AC: 664 AN: 2108

Alfa AF: 0.271 Hom.: 2003

Bravo AF: 0.289

Asia WGS AF: 0.136 AC: 471 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.56
PhyloP100		0.87
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: rs8008961; hg19: chr14-68752643;