rs2282001

Positions:

• chr9-35377775-G-C
• chr9-35377775-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):​c.10063+80G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,396,532 control chromosomes in the GnomAD database, including 11,917 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 0.17 (3171 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8746 hom.)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13B	NM_001371189.2	c.10063+80G>C		intron_variant		ENST00000635942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13B	ENST00000635942.2	c.10063+80G>C		intron_variant		5	NM_001371189.2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25191 AN: 152058 Hom.: 3151 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0755

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.100 AC: 124661 AN: 1244356 Hom.: 8746 AF XY: 0.101 AC XY: 62512 AN XY: 618592

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.0655

Gnomad4 EAS exome AF: 0.310

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0782

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.166 AC: 25246 AN: 152176 Hom.: 3171 Cov.: 32 AF XY: 0.168 AC XY: 12477 AN XY: 74410

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0620

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0968

Gnomad4 NFE AF: 0.0755

Gnomad4 OTH AF: 0.133

Alfa AF: 0.126 Hom.: 253

Bravo AF: 0.176

Asia WGS AF: 0.231 AC: 804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282001; hg19: chr9-35377772; COSMIC: COSV65934154;