rs12100794

Variant names:

• chr14-68570724-T-G
• rs12100794
• ENST00000487861.5:c.1037-40282T>G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-40282T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,338 control chromosomes in the GnomAD database, including 299 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 0.054 (299 hom., cov: 33)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-40282T>G		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1037-23761T>G		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321809.2	c.1037-31939T>G		intron_variant	Intron 10 of 11		NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-40282T>G		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-23761T>G		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-80057T>G		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8239 AN: 152220 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0590

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0258

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0449

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

GnomAD4 genome AF: 0.0542 AC: 8256 AN: 152338 Hom.: 299 Cov.: 33 AF XY: 0.0523 AC XY: 3900 AN XY: 74500

African (AFR) AF: 0.106 AC: 4387 AN: 41568

American (AMR) AF: 0.0414 AC: 634 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0590 AC: 205 AN: 3472

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5192

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4834

European-Finnish (FIN) AF: 0.0257 AC: 273 AN: 10620

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2494 AN: 68032

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.0428 Hom.: 296

Bravo AF: 0.0581

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12100794; hg19: chr14-69037441;