chr9-35295987-T-C

Variant names:

• chr9-35295987-T-C
• rs661712
• NM_001371189.2:c.761+57T>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.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
• Publications: 7 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=-0.87).
• 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 rank	MANE	Protein	UniProt
UNC13B	NM_001371189.2	c.761+57T>C		intron_variant	Intron 8 of 39	ENST00000635942.2	NP_001358118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC13B	ENST00000635942.2	c.761+57T>C		intron_variant	Intron 8 of 39	5	NM_001371189.2	ENSP00000490228.1

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

African (AFR) AF: 0.534 AC: 16347 AN: 30592

American (AMR) AF: 0.706 AC: 24550 AN: 34796

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 17567 AN: 24044

East Asian (EAS) AF: 0.580 AC: 20528 AN: 35416

South Asian (SAS) AF: 0.614 AC: 46218 AN: 75278

European-Finnish (FIN) AF: 0.699 AC: 34110 AN: 48800

Middle Eastern (MID) AF: 0.734 AC: 4073 AN: 5552

European-Non Finnish (NFE) AF: 0.686 AC: 710414 AN: 1036224

Other (OTH) AF: 0.668 AC: 37484 AN: 56082

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

African (AFR) AF: 0.537 AC: 22258 AN: 41472

American (AMR) AF: 0.694 AC: 10610 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2550 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2877 AN: 5158

South Asian (SAS) AF: 0.611 AC: 2944 AN: 4818

European-Finnish (FIN) AF: 0.700 AC: 7408 AN: 10582

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46600 AN: 67988

Other (OTH) AF: 0.666 AC: 1408 AN: 2114

Alfa AF: 0.651 Hom.: 4895

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
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs661712; hg19: chr9-35295984; COSMIC: COSV65932897;