rs661712

Positions:

• chr9-35295987-T-C
• chr9-35295987-T-G

Variant summary

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

The NM_001371189.2(UNC13B):​c.761+57T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,498,890 control chromosomes in the GnomAD database, including 341,267 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 0.64 (31755 hom., cov: 32)
  • Exomes 𝑓: 0.68 (309512 hom.)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC13B	NM_001371189.2	c.761+57T>C		intron_variant		ENST00000635942.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC13B	ENST00000635942.2	c.761+57T>C		intron_variant		5	NM_001371189.2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97501 AN: 151988 Hom.: 31739 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.665

GnomAD4 exome AF: 0.677 AC: 911291 AN: 1346784 Hom.: 309512 AF XY: 0.676 AC XY: 447887 AN XY: 663040

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.706

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.614

Gnomad4 FIN exome AF: 0.699

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome AF: 0.641 AC: 97549 AN: 152106 Hom.: 31755 Cov.: 32 AF XY: 0.643 AC XY: 47765 AN XY: 74342

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.694

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.666

Alfa AF: 0.654 Hom.: 4773

Bravo AF: 0.639

Asia WGS AF: 0.615 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs661712; hg19: chr9-35295984; COSMIC: COSV65932897;