rs12685290

Positions:

• chr9-35219056-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):​c.23-8959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,130 control chromosomes in the GnomAD database, including 23,204 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 0.55 (23204 hom., cov: 33)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.23-8959G>A		intron_variant		ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.23-8959G>A		intron_variant		5	NM_001371189.2	ENSP00000490228

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83402 AN: 152012 Hom.: 23188 Cov.: 33

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.549 AC: 83445 AN: 152130 Hom.: 23204 Cov.: 33 AF XY: 0.547 AC XY: 40664 AN XY: 74358

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.576

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.548

Alfa AF: 0.548 Hom.: 2874

Bravo AF: 0.544

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.79

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: rs12685290; hg19: chr9-35219053; COSMIC: COSV65932839;