rs8009944

Variant names:

• chr14-68572871-C-A
• rs8009944
• ENST00000487861.5:c.1037-38135C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68572871-C-A
• chr14-68572871-C-G
• chr14-68572871-C-T

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-38135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,020 control chromosomes in the GnomAD database, including 32,807 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 0.65 (32807 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937
• Publications: 17 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-38135C>A		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_133509.5	c.1037-21614C>A		intron_variant	Intron 10 of 10		NP_598193.2
RAD51B	NM_001321809.2	c.1037-29792C>A		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.1037-38135C>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-21614C>A		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-77910C>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98366 AN: 151902 Hom.: 32805 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.647 AC: 98382 AN: 152020 Hom.: 32807 Cov.: 32 AF XY: 0.646 AC XY: 47987 AN XY: 74292

African (AFR) AF: 0.526 AC: 21792 AN: 41436

American (AMR) AF: 0.654 AC: 9994 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2384 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1326 AN: 5160

South Asian (SAS) AF: 0.700 AC: 3372 AN: 4814

European-Finnish (FIN) AF: 0.695 AC: 7350 AN: 10576

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49809 AN: 67968

Other (OTH) AF: 0.655 AC: 1384 AN: 2114

Alfa AF: 0.701 Hom.: 154252

Bravo AF: 0.630

Asia WGS AF: 0.487 AC: 1692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.49
PhyloP100		0.94
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: rs8009944; hg19: chr14-69039588;