rs10136316

Variant names:

• chr14-68596804-C-T
• rs10136316
• ENST00000487861.5:c.1037-14202C>T

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-14202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,088 control chromosomes in the GnomAD database, including 11,107 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 0.38 (11107 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-14202C>T		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.1037-5859C>T		intron_variant	Intron 10 of 11		NP_001308738.1
RAD51B	NM_001321810.2	c.1037-5859C>T		intron_variant	Intron 10 of 10		NP_001308739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-14202C>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-53977C>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-86133C>T		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57216 AN: 151970 Hom.: 11102 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.376 AC: 57240 AN: 152088 Hom.: 11107 Cov.: 32 AF XY: 0.382 AC XY: 28373 AN XY: 74362

African (AFR) AF: 0.279 AC: 11586 AN: 41496

American (AMR) AF: 0.388 AC: 5926 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1124 AN: 3472

East Asian (EAS) AF: 0.530 AC: 2740 AN: 5172

South Asian (SAS) AF: 0.581 AC: 2797 AN: 4818

European-Finnish (FIN) AF: 0.420 AC: 4433 AN: 10564

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27284 AN: 67962

Other (OTH) AF: 0.386 AC: 815 AN: 2112

Alfa AF: 0.391 Hom.: 53047

Bravo AF: 0.365

Asia WGS AF: 0.528 AC: 1835 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	6.4
DANN	Benign	0.83
PhyloP100		0.14
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: rs10136316; hg19: chr14-69063521;