9-35213541-T-C

Variant names:

• chr9-35213541-T-C
• rs7036061
• NM_001371189.2:c.23-14474T>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.23-14474T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,024 control chromosomes in the GnomAD database, including 23,279 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 (23279 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371189.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	NM_001371189.2	MANE Select	c.23-14474T>C		intron	N/A	NP_001358118.1
	UNC13B	NM_001330653.3		c.23-14474T>C		intron	N/A	NP_001317582.1
	UNC13B	NM_001387551.1		c.23-14474T>C		intron	N/A	NP_001374480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.23-14474T>C		intron	N/A	ENSP00000490228.1
	UNC13B	ENST00000619578.4	TSL:1	c.23-14474T>C		intron	N/A	ENSP00000479261.1
	UNC13B	ENST00000378495.7	TSL:1	c.23-14474T>C		intron	N/A	ENSP00000367756.3

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83538 AN: 151906 Hom.: 23265 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.550 AC: 83574 AN: 152024 Hom.: 23279 Cov.: 31 AF XY: 0.549 AC XY: 40775 AN XY: 74298

African (AFR) AF: 0.530 AC: 21967 AN: 41456

American (AMR) AF: 0.477 AC: 7293 AN: 15274

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

East Asian (EAS) AF: 0.577 AC: 2986 AN: 5174

South Asian (SAS) AF: 0.547 AC: 2631 AN: 4806

European-Finnish (FIN) AF: 0.533 AC: 5631 AN: 10564

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39072 AN: 67960

Other (OTH) AF: 0.550 AC: 1161 AN: 2112

Alfa AF: 0.560 Hom.: 22689

Bravo AF: 0.545

Asia WGS AF: 0.575 AC: 1997 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.83
PhyloP100		-0.77
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: rs7036061; hg19: chr9-35213538; COSMIC: COSV65937974;