rs10438159

Variant names:

• chr14-68630655-C-T
• rs10438159
• ENST00000488612.5:c.1037-20126C>T

Variant summary

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

The ENST00000488612.5(RAD51B):​c.1037-20126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,140 control chromosomes in the GnomAD database, including 2,151 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 0.12 (2151 hom., cov: 31)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321818.2	c.1037-52282C>T		intron_variant	Intron 10 of 10		NP_001308747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000488612.5	c.1037-20126C>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-52282C>T		intron_variant	Intron 4 of 4	3
RAD51B	ENST00000553595.5	n.614-52282C>T		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18486 AN: 152022 Hom.: 2145 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0400

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0307

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.100

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

GnomAD4 genome AF: 0.122 AC: 18532 AN: 152140 Hom.: 2151 Cov.: 31 AF XY: 0.117 AC XY: 8734 AN XY: 74390

African (AFR) AF: 0.305 AC: 12621 AN: 41438

American (AMR) AF: 0.0646 AC: 988 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 139 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5178

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4822

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0559 AC: 3803 AN: 68014

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0754 Hom.: 591

Bravo AF: 0.129

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.75
PhyloP100		0.17
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: rs10438159; hg19: chr14-69097372;