rs12726

Positions:

• chr9-35404843-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001371189.2(UNC13B):​c.*810G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,600 control chromosomes in the GnomAD database, including 2,798 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 0.16 (2778 hom., cov: 31)
  • Exomes 𝑓: 0.25 (20 hom.)
• Consequence: UNC13B NM_001371189.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487

Genes affected

UNC13B (HGNC:12566): (unc-13 homolog B) This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13B	NM_001371189.2	c.*810G>A		3_prime_UTR_variant	40/40	ENST00000635942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13B	ENST00000635942.2	c.*810G>A		3_prime_UTR_variant	40/40	5	NM_001371189.2

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24699 AN: 152002 Hom.: 2778 Cov.: 31

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.248 AC: 119 AN: 480 Hom.: 20 Cov.: 0 AF XY: 0.245 AC XY: 73 AN XY: 298

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.162 AC: 24694 AN: 152120 Hom.: 2778 Cov.: 31 AF XY: 0.159 AC XY: 11848 AN XY: 74364

Gnomad4 AFR AF: 0.0418

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.167

Alfa AF: 0.221 Hom.: 5242

Bravo AF: 0.151

Asia WGS AF: 0.0270 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.9
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs12726; hg19: chr9-35404840; COSMIC: COSV61468632; COSMIC: COSV61468632;