rs4879877

chr9-35181294-G-Achr9-35181294-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):c.22+18989G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,106 control chromosomes in the GnomAD database, including 51,281 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 0.82 (51281 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13B	NM_001371189.2	c.22+18989G>A		intron_variant		ENST00000635942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13B	ENST00000635942.2	c.22+18989G>A		intron_variant		5	NM_001371189.2

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124535 AN: 151988 Hom.: 51264 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.819 AC: 124594 AN: 152106 Hom.: 51281 Cov.: 31 AF XY: 0.819 AC XY: 60922 AN XY: 74358

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.982

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.821

Alfa AF: 0.822 Hom.: 7614

Bravo AF: 0.812

Asia WGS AF: 0.887 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	4.9
Dann	Benign	0.45

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: rs4879877; hg19: chr9-35181291;