rs2525507

chr14-68471647-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133510.4(RAD51B):c.1036+3397A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 150,332 control chromosomes in the GnomAD database, including 1,854 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 0.14 (1854 hom., cov: 27)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.1036+3397A>G		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.1036+3397A>G		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21274 AN: 150226 Hom.: 1855 Cov.: 27

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.141 AC: 21261 AN: 150332 Hom.: 1854 Cov.: 27 AF XY: 0.141 AC XY: 10302 AN XY: 73240

Gnomad4 AFR AF: 0.0504

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.187

Alfa AF: 0.158 Hom.: 398

Bravo AF: 0.139

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	8.4
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2525507; hg19: chr14-68938364;