rs4899234

Variant names:

• chr14-68264492-G-A
• rs4899234
• NM_133510.4:c.757-27392G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-68264492-G-A
• chr14-68264492-G-C

Variant summary

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

The ENST00000471583.6(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 ENST00000471583.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153
• Publications: 5 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 (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471583.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.757-27392G>A		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.757-27392G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.757-27392G>A		intron	N/A	NP_598193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.757-27392G>A		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.757-27392G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.757-27392G>A		intron	N/A	ENSP00000419471.1

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

African (AFR) AF: 0.0315 AC: 1307 AN: 41556

American (AMR) AF: 0.101 AC: 1547 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1168 AN: 5176

South Asian (SAS) AF: 0.122 AC: 591 AN: 4830

European-Finnish (FIN) AF: 0.0824 AC: 875 AN: 10618

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0654 AC: 4450 AN: 68016

Other (OTH) AF: 0.0685 AC: 145 AN: 2116

Alfa AF: 0.0695 Hom.: 227

Bravo AF: 0.0689

Asia WGS AF: 0.166 AC: 576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.59
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4899234; hg19: chr14-68731209;