rs4902566

Variant names:

• chr14-68326837-T-C
• rs4902566
• NM_133510.4:c.853+34857T>C

Variant summary

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

The NM_133510.4(RAD51B):​c.853+34857T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 152,040 control chromosomes in the GnomAD database, including 35,034 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 0.68 (35034 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 8 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133510.4. 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.853+34857T>C		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.853+34857T>C		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.853+34857T>C		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.853+34857T>C		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.853+34857T>C		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.853+34857T>C		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.676 AC: 102743 AN: 151922 Hom.: 35011 Cov.: 32

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.676 AC: 102808 AN: 152040 Hom.: 35034 Cov.: 32 AF XY: 0.673 AC XY: 50047 AN XY: 74332

African (AFR) AF: 0.612 AC: 25332 AN: 41426

American (AMR) AF: 0.693 AC: 10588 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2147 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2606 AN: 5176

South Asian (SAS) AF: 0.678 AC: 3268 AN: 4820

European-Finnish (FIN) AF: 0.691 AC: 7299 AN: 10558

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49337 AN: 67986

Other (OTH) AF: 0.646 AC: 1364 AN: 2112

Alfa AF: 0.702 Hom.: 49287

Bravo AF: 0.667

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.16
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: rs4902566; hg19: chr14-68793554;