NM_133510.4:c.757-27143A>G

Variant names:

• chr14-68264741-A-G
• rs4902562
• NM_133510.4:c.757-27143A>G

Variant summary

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

The NM_133510.4(RAD51B):​c.757-27143A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,064 control chromosomes in the GnomAD database, including 33,233 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 0.64 (33233 hom., cov: 31)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 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.757-27143A>G		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.757-27143A>G		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.757-27143A>G		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.757-27143A>G		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.757-27143A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.757-27143A>G		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97703 AN: 151946 Hom.: 33198 Cov.: 31

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.643 AC: 97785 AN: 152064 Hom.: 33233 Cov.: 31 AF XY: 0.639 AC XY: 47498 AN XY: 74322

African (AFR) AF: 0.869 AC: 36051 AN: 41484

American (AMR) AF: 0.536 AC: 8197 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3472

East Asian (EAS) AF: 0.350 AC: 1812 AN: 5174

South Asian (SAS) AF: 0.420 AC: 2023 AN: 4822

European-Finnish (FIN) AF: 0.610 AC: 6432 AN: 10540

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38930 AN: 67968

Other (OTH) AF: 0.640 AC: 1350 AN: 2110

Alfa AF: 0.579 Hom.: 62330

Bravo AF: 0.651

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.32
PhyloP100		-1.5
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: rs4902562; hg19: chr14-68731458;