rs11628885

Variant names:

• chr14-68258073-A-G
• rs11628885
• NM_133510.4:c.757-33811A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):​c.757-33811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,162 control chromosomes in the GnomAD database, including 1,173 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 0.11 (1173 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.757-33811A>G		intron_variant	Intron 7 of 10	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-33811A>G		intron_variant	Intron 7 of 10	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16433 AN: 152044 Hom.: 1172 Cov.: 31

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.108 AC: 16425 AN: 152162 Hom.: 1173 Cov.: 31 AF XY: 0.108 AC XY: 8053 AN XY: 74388

African (AFR) AF: 0.0278 AC: 1156 AN: 41538

American (AMR) AF: 0.131 AC: 1998 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3468

East Asian (EAS) AF: 0.00810 AC: 42 AN: 5182

South Asian (SAS) AF: 0.154 AC: 744 AN: 4820

European-Finnish (FIN) AF: 0.113 AC: 1198 AN: 10572

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9895 AN: 67984

Other (OTH) AF: 0.136 AC: 287 AN: 2114

Alfa AF: 0.116 Hom.: 143

Bravo AF: 0.106

Asia WGS AF: 0.0900 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.87
PhyloP100		0.98
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: rs11628885; hg19: chr14-68724790;