rs1927962

Variant names:

• chr9-35387169-A-G
• rs1927962
• NM_001371189.2:c.11094+876A>G

Variant summary

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

The NM_001371189.2(UNC13B):​c.11094+876A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,138 control chromosomes in the GnomAD database, including 2,830 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 0.19 (2830 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.11094+876A>G		intron_variant	Intron 24 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.11094+876A>G		intron_variant	Intron 24 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28748 AN: 152020 Hom.: 2831 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.189 AC: 28767 AN: 152138 Hom.: 2830 Cov.: 32 AF XY: 0.190 AC XY: 14139 AN XY: 74374

African (AFR) AF: 0.157 AC: 6531 AN: 41514

American (AMR) AF: 0.194 AC: 2964 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.159 AC: 822 AN: 5186

South Asian (SAS) AF: 0.213 AC: 1026 AN: 4824

European-Finnish (FIN) AF: 0.209 AC: 2209 AN: 10570

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13763 AN: 67968

Other (OTH) AF: 0.202 AC: 428 AN: 2114

Alfa AF: 0.195 Hom.: 6240

Bravo AF: 0.186

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.60
PhyloP100		0.29
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: rs1927962; hg19: chr9-35387166; COSMIC: COSV65938015;