9-35188820-A-T

Variant names:

• chr9-35188820-A-T
• rs4111859
• NM_001371189.2:c.22+26515A>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.22+26515A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 152,168 control chromosomes in the GnomAD database, including 51,633 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 (51633 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.940
• 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=-0.98).
• 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 rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.22+26515A>T		intron_variant	Intron 1 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.22+26515A>T		intron_variant	Intron 1 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124990 AN: 152050 Hom.: 51608 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.822

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

GnomAD4 genome AF: 0.822 AC: 125062 AN: 152168 Hom.: 51633 Cov.: 32 AF XY: 0.822 AC XY: 61183 AN XY: 74396

African (AFR) AF: 0.782 AC: 32451 AN: 41504

American (AMR) AF: 0.746 AC: 11391 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2878 AN: 3472

East Asian (EAS) AF: 0.982 AC: 5101 AN: 5192

South Asian (SAS) AF: 0.863 AC: 4162 AN: 4824

European-Finnish (FIN) AF: 0.811 AC: 8587 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57678 AN: 68002

Other (OTH) AF: 0.824 AC: 1740 AN: 2112

Alfa AF: 0.789 Hom.: 2780

Bravo AF: 0.815

Asia WGS AF: 0.902 AC: 3134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.4
DANN	Benign	0.46
PhyloP100		-0.94
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: rs4111859; hg19: chr9-35188817;