rs2145157

Variant names:

• chr14-68600921-A-G
• rs2145157
• ENST00000487861.5:c.1037-10085A>G

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-10085A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,010 control chromosomes in the GnomAD database, including 9,492 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 0.35 (9492 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487861.5. 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_001321821.2		c.1037-10085A>G		intron	N/A	NP_001308750.1
	RAD51B	NM_001321809.2		c.1037-1742A>G		intron	N/A	NP_001308738.1
	RAD51B	NM_001321810.2		c.1037-1742A>G		intron	N/A	NP_001308739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-10085A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-49860A>G		intron	N/A	ENSP00000420061.1
	RAD51B	ENST00000478014.5	TSL:3	n.384-82016A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52513 AN: 151892 Hom.: 9488 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.346 AC: 52538 AN: 152010 Hom.: 9492 Cov.: 32 AF XY: 0.344 AC XY: 25544 AN XY: 74304

African (AFR) AF: 0.307 AC: 12722 AN: 41432

American (AMR) AF: 0.298 AC: 4559 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1226 AN: 3472

East Asian (EAS) AF: 0.178 AC: 922 AN: 5176

South Asian (SAS) AF: 0.164 AC: 792 AN: 4820

European-Finnish (FIN) AF: 0.437 AC: 4610 AN: 10552

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26566 AN: 67956

Other (OTH) AF: 0.328 AC: 694 AN: 2116

Alfa AF: 0.369 Hom.: 47489

Bravo AF: 0.333

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.5
DANN	Benign	0.67
PhyloP100		0.080
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: rs2145157; hg19: chr14-69067638;