rs7040048

Positions:

• chr9-35253679-A-G

Variant summary

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

The NM_001371189.2(UNC13B):​c.469-5314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,180 control chromosomes in the GnomAD database, including 1,868 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 0.15 (1868 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13B	NM_001371189.2	c.469-5314A>G		intron_variant		ENST00000635942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13B	ENST00000635942.2	c.469-5314A>G		intron_variant		5	NM_001371189.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22112 AN: 152062 Hom.: 1863 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0782

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.145 AC: 22126 AN: 152180 Hom.: 1868 Cov.: 31 AF XY: 0.146 AC XY: 10834 AN XY: 74400

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.158

Alfa AF: 0.155 Hom.: 887

Bravo AF: 0.149

Asia WGS AF: 0.0800 AC: 279 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	3.2
DANN	Benign	0.43

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: rs7040048; hg19: chr9-35253676;