chr14-68589082-G-A

Variant names:

• chr14-68589082-G-A
• rs10483814
• ENST00000487861.5:c.1037-21924G>A

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-21924G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0726 in 152,210 control chromosomes in the GnomAD database, including 558 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 0.073 (558 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 3 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 (SAS) allele frequency at 95% confidence interval = 0.211 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.1037-21924G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.1037-5403G>A		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-13581G>A		intron	N/A	NP_001308738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-21924G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1037-5403G>A		intron	N/A	ENSP00000419471.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-61699G>A		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11064 AN: 152092 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0675

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0927

Gnomad OTH AF: 0.0849

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

GnomAD4 genome AF: 0.0726 AC: 11058 AN: 152210 Hom.: 558 Cov.: 32 AF XY: 0.0732 AC XY: 5451 AN XY: 74432

African (AFR) AF: 0.0305 AC: 1267 AN: 41532

American (AMR) AF: 0.0674 AC: 1032 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5186

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4818

European-Finnish (FIN) AF: 0.0505 AC: 535 AN: 10596

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0926 AC: 6299 AN: 67990

Other (OTH) AF: 0.0840 AC: 177 AN: 2108

Alfa AF: 0.0890 Hom.: 1178

Bravo AF: 0.0668

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.62
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: rs10483814; hg19: chr14-69055799;