rs12685290

Variant names:

• chr9-35219056-G-A
• rs12685290
• NM_001371189.2:c.23-8959G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.23-8959G>A		intron_variant	Intron 1 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.23-8959G>A		intron_variant	Intron 1 of 39	5	NM_001371189.2	ENSP00000490228.1

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

African (AFR) AF: 0.528 AC: 21934 AN: 41508

American (AMR) AF: 0.478 AC: 7302 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2011 AN: 3472

East Asian (EAS) AF: 0.576 AC: 2985 AN: 5182

South Asian (SAS) AF: 0.542 AC: 2612 AN: 4820

European-Finnish (FIN) AF: 0.523 AC: 5521 AN: 10552

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39102 AN: 67998

Other (OTH) AF: 0.548 AC: 1158 AN: 2112

Alfa AF: 0.549 Hom.: 2995

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
PhyloP100		-2.8
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: rs12685290; hg19: chr9-35219053; COSMIC: COSV65932839;