9-35381507-C-T

Variant names:

• chr9-35381507-C-T
• rs2281999
• NM_001371189.2:c.10492-49C>T

Variant summary

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

The NM_001371189.2(UNC13B):​c.10492-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 1,554,452 control chromosomes in the GnomAD database, including 90,491 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 0.38 (11805 hom., cov: 32)
  • Exomes 𝑓: 0.33 (78686 hom.)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.10492-49C>T		intron_variant	Intron 19 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.10492-49C>T		intron_variant	Intron 19 of 39	5	NM_001371189.2	ENSP00000490228.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57657 AN: 151888 Hom.: 11767 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.352

GnomAD3 exomes AF: 0.346 AC: 72214 AN: 208824 Hom.: 12945 AF XY: 0.347 AC XY: 39035 AN XY: 112488

Gnomad AFR exome AF: 0.531

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.437

Gnomad SAS exome AF: 0.447

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.310

GnomAD4 exome AF: 0.331 AC: 463562 AN: 1402448 Hom.: 78686 Cov.: 31 AF XY: 0.333 AC XY: 230162 AN XY: 691404

Gnomad4 AFR exome AF: 0.533

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.424

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.316

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.380 AC: 57742 AN: 152004 Hom.: 11805 Cov.: 32 AF XY: 0.379 AC XY: 28164 AN XY: 74286

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.351

Alfa AF: 0.320 Hom.: 7959

Bravo AF: 0.382

Asia WGS AF: 0.422 AC: 1468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.73

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: rs2281999; hg19: chr9-35381504;