rs17105965

Variant names:

• chr14-68602877-T-C
• rs17105965
• ENST00000487861.5:c.1037-8129T>C

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-8129T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,150 control chromosomes in the GnomAD database, including 1,957 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 0.15 (1957 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321810.2	c.*207T>C		3_prime_UTR_variant	Exon 11 of 11		NP_001308739.1
RAD51B	NM_001321821.2	c.1037-8129T>C		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.*33+174T>C		intron_variant	Intron 11 of 11		NP_001308738.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-8129T>C		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-47904T>C		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-80060T>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23342 AN: 152032 Hom.: 1956 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.153 AC: 23353 AN: 152150 Hom.: 1957 Cov.: 32 AF XY: 0.154 AC XY: 11425 AN XY: 74398

African (AFR) AF: 0.187 AC: 7750 AN: 41484

American (AMR) AF: 0.119 AC: 1815 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3472

East Asian (EAS) AF: 0.0602 AC: 312 AN: 5182

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2184 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10068 AN: 67994

Other (OTH) AF: 0.152 AC: 320 AN: 2110

Alfa AF: 0.146 Hom.: 3229

Bravo AF: 0.148

Asia WGS AF: 0.0750 AC: 263 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	6.0
DANN	Benign	0.71
PhyloP100		0.64
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: rs17105965; hg19: chr14-69069594;