NM_133510.4:c.453-9223G>A

Variant names:

• chr14-67876646-G-A
• rs1950764
• NM_133510.4:c.453-9223G>A

Variant summary

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

The NM_133510.4(RAD51B):​c.453-9223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,216 control chromosomes in the GnomAD database, including 1,579 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 0.12 (1579 hom., cov: 32)
• Consequence: RAD51B NM_133510.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 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.453-9223G>A		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.453-9223G>A		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.453-9223G>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.453-9223G>A		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.453-9223G>A		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.453-9223G>A		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18855 AN: 152098 Hom.: 1581 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.00654

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.124 AC: 18841 AN: 152216 Hom.: 1579 Cov.: 32 AF XY: 0.124 AC XY: 9217 AN XY: 74420

African (AFR) AF: 0.0312 AC: 1296 AN: 41554

American (AMR) AF: 0.142 AC: 2163 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 895 AN: 3470

East Asian (EAS) AF: 0.00655 AC: 34 AN: 5188

South Asian (SAS) AF: 0.176 AC: 851 AN: 4830

European-Finnish (FIN) AF: 0.129 AC: 1372 AN: 10602

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11696 AN: 67994

Other (OTH) AF: 0.145 AC: 306 AN: 2112

Alfa AF: 0.160 Hom.: 2565

Bravo AF: 0.120

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.6
DANN	Benign	0.76
PhyloP100		0.0060
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: rs1950764; hg19: chr14-68343363;