rs12684897

Variant names:

• chr9-35369128-T-C
• rs12684897
• NM_001371189.2:c.9462-1190T>C

Variant summary

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

The NM_001371189.2(UNC13B):​c.9462-1190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,226 control chromosomes in the GnomAD database, including 2,061 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 (2061 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 3 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.9462-1190T>C		intron_variant	Intron 12 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.9462-1190T>C		intron_variant	Intron 12 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24298 AN: 152108 Hom.: 2059 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.160 AC: 24308 AN: 152226 Hom.: 2061 Cov.: 32 AF XY: 0.159 AC XY: 11820 AN XY: 74416

African (AFR) AF: 0.137 AC: 5683 AN: 41530

American (AMR) AF: 0.175 AC: 2683 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 747 AN: 3470

East Asian (EAS) AF: 0.154 AC: 796 AN: 5184

South Asian (SAS) AF: 0.104 AC: 502 AN: 4826

European-Finnish (FIN) AF: 0.159 AC: 1687 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11652 AN: 68014

Other (OTH) AF: 0.178 AC: 376 AN: 2114

Alfa AF: 0.169 Hom.: 2715

Bravo AF: 0.161

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.093
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: rs12684897; hg19: chr9-35369125;