rs10814227

Variant names:

• chr9-35330611-G-A
• rs10814227
• NM_001371189.2:c.9414+16622G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35330611-G-A
• chr9-35330611-G-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.9414+16622G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,114 control chromosomes in the GnomAD database, including 10,103 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 0.36 (10103 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.9414+16622G>A		intron_variant	Intron 11 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.9414+16622G>A		intron_variant	Intron 11 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54085 AN: 151996 Hom.: 10070 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.356 AC: 54162 AN: 152114 Hom.: 10103 Cov.: 32 AF XY: 0.355 AC XY: 26389 AN XY: 74358

African (AFR) AF: 0.457 AC: 18983 AN: 41506

American (AMR) AF: 0.305 AC: 4665 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 913 AN: 3468

East Asian (EAS) AF: 0.443 AC: 2288 AN: 5168

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3161 AN: 10566

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21333 AN: 67992

Other (OTH) AF: 0.331 AC: 699 AN: 2112

Alfa AF: 0.340 Hom.: 3434

Bravo AF: 0.359

Asia WGS AF: 0.379 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		0.38
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: rs10814227; hg19: chr9-35330608;