chr14-68653426-G-A

Variant names:

• chr14-68653426-G-A
• rs10483818
• ENST00000488612.5:c.*11+2570G>A

Variant summary

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

The ENST00000488612.5(RAD51B):​c.*11+2570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 152,248 control chromosomes in the GnomAD database, including 579 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 0.077 (579 hom., cov: 33)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 2 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

ENSG00000258623 (HGNC:58171):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321818.2	c.1037-29511G>A		intron_variant	Intron 10 of 10		NP_001308747.1
RAD51B-AS1	XR_007064220.1	n.189-758C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.*11+2570G>A		intron_variant	Intron 11 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-29511G>A		intron_variant	Intron 4 of 4	3
RAD51B	ENST00000553595.5	n.614-29511G>A		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11741 AN: 152130 Hom.: 580 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0429

Gnomad OTH AF: 0.0841

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

GnomAD4 genome AF: 0.0772 AC: 11747 AN: 152248 Hom.: 579 Cov.: 33 AF XY: 0.0786 AC XY: 5853 AN XY: 74434

African (AFR) AF: 0.126 AC: 5248 AN: 41522

American (AMR) AF: 0.0695 AC: 1063 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3472

East Asian (EAS) AF: 0.109 AC: 565 AN: 5184

South Asian (SAS) AF: 0.125 AC: 603 AN: 4822

European-Finnish (FIN) AF: 0.0847 AC: 898 AN: 10606

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0429 AC: 2917 AN: 68034

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0520 Hom.: 581

Bravo AF: 0.0771

Asia WGS AF: 0.116 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.80
PhyloP100		-0.76
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: rs10483818; hg19: chr14-69120143;