9-35234598-G-A

Variant names:

• chr9-35234598-G-A
• rs17360668
• NM_001371189.2:c.153-1871G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):​c.153-1871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,066 control chromosomes in the GnomAD database, including 2,877 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 0.18 (2877 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.795
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.153-1871G>A		intron_variant	Intron 3 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.153-1871G>A		intron_variant	Intron 3 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27803 AN: 151948 Hom.: 2875 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.183 AC: 27811 AN: 152066 Hom.: 2877 Cov.: 32 AF XY: 0.179 AC XY: 13332 AN XY: 74344

African (AFR) AF: 0.100 AC: 4161 AN: 41462

American (AMR) AF: 0.169 AC: 2579 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3470

East Asian (EAS) AF: 0.105 AC: 546 AN: 5184

South Asian (SAS) AF: 0.166 AC: 799 AN: 4816

European-Finnish (FIN) AF: 0.205 AC: 2163 AN: 10576

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16199 AN: 67970

Other (OTH) AF: 0.196 AC: 414 AN: 2112

Alfa AF: 0.216 Hom.: 2007

Bravo AF: 0.176

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.67
PhyloP100		0.80
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: rs17360668; hg19: chr9-35234595;