9-35244064-A-T

Variant names:

• chr9-35244064-A-T
• rs7851161
• NM_001371189.2:c.468+700A>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.468+700A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,916 control chromosomes in the GnomAD database, including 11,370 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 0.37 (11370 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.468+700A>T		intron_variant	Intron 6 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.468+700A>T		intron_variant	Intron 6 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56037 AN: 151800 Hom.: 11366 Cov.: 31

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.392

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

GnomAD4 genome AF: 0.369 AC: 56052 AN: 151916 Hom.: 11370 Cov.: 31 AF XY: 0.369 AC XY: 27373 AN XY: 74232

African (AFR) AF: 0.222 AC: 9206 AN: 41460

American (AMR) AF: 0.367 AC: 5593 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1631 AN: 3468

East Asian (EAS) AF: 0.191 AC: 984 AN: 5158

South Asian (SAS) AF: 0.374 AC: 1797 AN: 4808

European-Finnish (FIN) AF: 0.446 AC: 4710 AN: 10556

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30705 AN: 67906

Other (OTH) AF: 0.394 AC: 829 AN: 2106

Alfa AF: 0.289 Hom.: 929

Bravo AF: 0.354

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.8
DANN	Benign	0.69
PhyloP100		0.74
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: rs7851161; hg19: chr9-35244061; COSMIC: COSV65932855; COSMIC: COSV65932855;