9-35263724-G-T

Variant names:

• chr9-35263724-G-T
• rs10758301
• NM_001371189.2:c.526+4674G>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.526+4674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 151,854 control chromosomes in the GnomAD database, including 22,507 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 0.54 (22507 hom., cov: 30)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 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.526+4674G>T		intron	N/A	NP_001358118.1
	UNC13B	NM_001330653.3		c.526+4674G>T		intron	N/A	NP_001317582.1
	UNC13B	NM_001387551.1		c.526+4674G>T		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.526+4674G>T		intron	N/A	ENSP00000490228.1
	UNC13B	ENST00000619578.4	TSL:1	c.526+4674G>T		intron	N/A	ENSP00000479261.1
	UNC13B	ENST00000378495.7	TSL:1	c.526+4674G>T		intron	N/A	ENSP00000367756.3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82006 AN: 151736 Hom.: 22493 Cov.: 30

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.540 AC: 82045 AN: 151854 Hom.: 22507 Cov.: 30 AF XY: 0.538 AC XY: 39926 AN XY: 74200

African (AFR) AF: 0.518 AC: 21446 AN: 41386

American (AMR) AF: 0.473 AC: 7203 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2007 AN: 3468

East Asian (EAS) AF: 0.549 AC: 2833 AN: 5164

South Asian (SAS) AF: 0.489 AC: 2351 AN: 4812

European-Finnish (FIN) AF: 0.519 AC: 5461 AN: 10514

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.571 AC: 38799 AN: 67964

Other (OTH) AF: 0.536 AC: 1129 AN: 2108

Alfa AF: 0.557 Hom.: 9989

Bravo AF: 0.537

Asia WGS AF: 0.534 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.49
PhyloP100		0.20
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: rs10758301; hg19: chr9-35263721; COSMIC: COSV65932874;