rs10972397

Variant names:

• chr9-35241486-A-G
• rs10972397
• NM_001371189.2:c.395-1805A>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.395-1805A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,662 control chromosomes in the GnomAD database, including 1,849 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 0.14 (1849 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.395-1805A>G		intron_variant	Intron 5 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.395-1805A>G		intron_variant	Intron 5 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21976 AN: 151544 Hom.: 1844 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.145 AC: 21990 AN: 151662 Hom.: 1849 Cov.: 31 AF XY: 0.145 AC XY: 10733 AN XY: 74070

African (AFR) AF: 0.102 AC: 4212 AN: 41324

American (AMR) AF: 0.247 AC: 3747 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3466

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5170

South Asian (SAS) AF: 0.135 AC: 649 AN: 4812

European-Finnish (FIN) AF: 0.180 AC: 1885 AN: 10480

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10434 AN: 67940

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.156 Hom.: 260

Bravo AF: 0.149

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.55
PhyloP100		0.081
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: rs10972397; hg19: chr9-35241483;