rs4899234

chr14-68264492-G-Achr14-68264492-G-C

Variant summary

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

The NM_133510.4(RAD51B):c.757-27392G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0685 in 152,280 control chromosomes in the GnomAD database, including 505 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 0.068 (505 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51B	NM_133510.4	c.757-27392G>A		intron_variant		ENST00000471583.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000471583.6	c.757-27392G>A		intron_variant		1	NM_133510.4	P4

Frequencies

GnomAD3 genomes AF: 0.0685 AC: 10430 AN: 152160 Hom.: 506 Cov.: 32

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0654

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0685 AC: 10429 AN: 152280 Hom.: 505 Cov.: 32 AF XY: 0.0718 AC XY: 5344 AN XY: 74460

Gnomad4 AFR AF: 0.0315

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0654

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0707 Hom.: 148

Bravo AF: 0.0689

Asia WGS AF: 0.166 AC: 576 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	3.1
Dann	Benign	0.59

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: rs4899234; hg19: chr14-68731209;