rs2525507

Variant names:

• chr14-68471647-A-G
• rs2525507
• NM_133510.4:c.1036+3397A>G

Variant summary

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

The NM_001321819.1(RAD51B):​c.*1114A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 150,332 control chromosomes in the GnomAD database, including 1,854 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 0.14 (1854 hom., cov: 27)
• Consequence: RAD51B NM_001321819.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 3 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=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321819.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	NM_133510.4	MANE Select	c.1036+3397A>G		intron	N/A	NP_598194.1
	RAD51B	NM_001321819.1		c.*1114A>G		3_prime_UTR	Exon 11 of 11	NP_001308748.1
	RAD51B	NM_001321821.2		c.1036+3397A>G		intron	N/A	NP_001308750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.1036+3397A>G		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.1036+3397A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1036+3397A>G		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21274 AN: 150226 Hom.: 1855 Cov.: 27

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.141 AC: 21261 AN: 150332 Hom.: 1854 Cov.: 27 AF XY: 0.141 AC XY: 10302 AN XY: 73240

African (AFR) AF: 0.0504 AC: 2065 AN: 40944

American (AMR) AF: 0.152 AC: 2273 AN: 14986

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3466

East Asian (EAS) AF: 0.0301 AC: 152 AN: 5048

South Asian (SAS) AF: 0.139 AC: 658 AN: 4730

European-Finnish (FIN) AF: 0.155 AC: 1568 AN: 10144

Middle Eastern (MID) AF: 0.266 AC: 77 AN: 290

European-Non Finnish (NFE) AF: 0.191 AC: 12913 AN: 67728

Other (OTH) AF: 0.187 AC: 391 AN: 2088

Alfa AF: 0.166 Hom.: 3613

Bravo AF: 0.139

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.4
DANN	Benign	0.72
PhyloP100		-0.35
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: rs2525507; hg19: chr14-68938364;