9-35269822-T-C

Variant names:

• chr9-35269822-T-C
• rs10121009
• NM_001371189.2:c.526+10772T>C

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+10772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,088 control chromosomes in the GnomAD database, including 38,391 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 0.70 (38391 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.526+10772T>C		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+10772T>C		intron_variant	Intron 7 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106217 AN: 151970 Hom.: 38385 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.699 AC: 106251 AN: 152088 Hom.: 38391 Cov.: 31 AF XY: 0.697 AC XY: 51781 AN XY: 74342

African (AFR) AF: 0.511 AC: 21181 AN: 41466

American (AMR) AF: 0.745 AC: 11383 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2850 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2861 AN: 5176

South Asian (SAS) AF: 0.708 AC: 3411 AN: 4818

European-Finnish (FIN) AF: 0.748 AC: 7902 AN: 10570

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54093 AN: 67992

Other (OTH) AF: 0.728 AC: 1537 AN: 2110

Alfa AF: 0.769 Hom.: 51042

Bravo AF: 0.691

Asia WGS AF: 0.640 AC: 2229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.70
PhyloP100		0.62
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: rs10121009; hg19: chr9-35269819; COSMIC: COSV65932880;