9-35166766-G-T

Variant names:

• chr9-35166766-G-T
• rs13293564
• NM_001371189.2:c.22+4461G>T

Variant summary

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

The NM_001371189.2(UNC13B):​c.22+4461G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,026 control chromosomes in the GnomAD database, including 16,288 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 0.45 (16288 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 20 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.22+4461G>T		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.22+4461G>T		intron_variant	Intron 1 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67660 AN: 151908 Hom.: 16271 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.445 AC: 67715 AN: 152026 Hom.: 16288 Cov.: 32 AF XY: 0.438 AC XY: 32561 AN XY: 74302

African (AFR) AF: 0.590 AC: 24451 AN: 41448

American (AMR) AF: 0.461 AC: 7047 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5180

South Asian (SAS) AF: 0.202 AC: 973 AN: 4824

European-Finnish (FIN) AF: 0.467 AC: 4921 AN: 10542

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27598 AN: 67964

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.410 Hom.: 55668

Bravo AF: 0.450

Asia WGS AF: 0.146 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.55
PhyloP100		-1.3
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: rs13293564; hg19: chr9-35166763; COSMIC: COSV65932793;