14-68615200-G-T

Variant names:

• chr14-68615200-G-T
• rs2331779
• ENST00000488612.5:c.1037-35581G>T

Variant summary

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

The ENST00000488612.5(RAD51B):​c.1037-35581G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,144 control chromosomes in the GnomAD database, including 3,699 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 0.20 (3699 hom., cov: 33)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500
• Publications: 2 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

ENSG00000306917 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488612.5. 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_001321818.2		c.1037-67737G>T		intron	N/A	NP_001308747.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000488612.5	TSL:1	c.1037-35581G>T		intron	N/A	ENSP00000420061.1
	RAD51B	ENST00000478014.5	TSL:3	n.384-67737G>T		intron	N/A
	RAD51B	ENST00000553595.5	TSL:3	n.614-67737G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30895 AN: 152026 Hom.: 3680 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0277

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.203 AC: 30961 AN: 152144 Hom.: 3699 Cov.: 33 AF XY: 0.199 AC XY: 14814 AN XY: 74372

African (AFR) AF: 0.327 AC: 13554 AN: 41470

American (AMR) AF: 0.159 AC: 2427 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.0280 AC: 145 AN: 5186

South Asian (SAS) AF: 0.149 AC: 720 AN: 4832

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11517 AN: 68008

Other (OTH) AF: 0.206 AC: 436 AN: 2112

Alfa AF: 0.183 Hom.: 1493

Bravo AF: 0.210

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.80
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2331779; hg19: chr14-69081917;