rs10114937

Variant names:

• chr9-35271820-C-T
• rs10114937
• NM_001371189.2:c.526+12770C>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.526+12770C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,106 control chromosomes in the GnomAD database, including 30,740 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 0.63 (30740 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.526+12770C>T		intron_variant	Intron 7 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.526+12770C>T		intron_variant	Intron 7 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95577 AN: 151988 Hom.: 30733 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.655

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

GnomAD4 genome AF: 0.629 AC: 95611 AN: 152106 Hom.: 30740 Cov.: 32 AF XY: 0.630 AC XY: 46859 AN XY: 74336

African (AFR) AF: 0.491 AC: 20354 AN: 41478

American (AMR) AF: 0.686 AC: 10492 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2539 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2854 AN: 5172

South Asian (SAS) AF: 0.614 AC: 2958 AN: 4814

European-Finnish (FIN) AF: 0.701 AC: 7407 AN: 10560

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.687 AC: 46726 AN: 68004

Other (OTH) AF: 0.656 AC: 1387 AN: 2114

Alfa AF: 0.680 Hom.: 54275

Bravo AF: 0.624

Asia WGS AF: 0.603 AC: 2098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.82
PhyloP100		-0.076
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: rs10114937; hg19: chr9-35271817; COSMIC: COSV65937983;