9-35263724-G-T

Position:

• chr9-35263724-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

UNC13B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.526+4674G>T		intron_variant		ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.526+4674G>T		intron_variant		5	NM_001371189.2	ENSP00000490228.1

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

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.536

Alfa AF: 0.552 Hom.: 5266

Bravo AF: 0.537

Asia WGS AF: 0.534 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.57
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs10758301; hg19: chr9-35263721; COSMIC: COSV65932874;