rs2282001

Variant names:

• chr9-35377775-G-C
• rs2282001
• NM_001371189.2:c.10063+80G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371189.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	NM_001371189.2	MANE Select	c.10063+80G>C		intron	N/A	NP_001358118.1	A0A1B0GUS7
	UNC13B	NM_001371187.2		c.2956+80G>C		intron	N/A	NP_001358116.1	A0A1B0GVW8
	UNC13B	NM_001387555.1		c.2956+80G>C		intron	N/A	NP_001374484.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.10063+80G>C		intron	N/A	ENSP00000490228.1	A0A1B0GUS7
	UNC13B	ENST00000619578.4	TSL:1	c.1816+80G>C		intron	N/A	ENSP00000479261.1	O14795-2
	UNC13B	ENST00000378495.7	TSL:1	c.1816+80G>C		intron	N/A	ENSP00000367756.3	O14795-1

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

African (AFR) AF: 0.351 AC: 9986 AN: 28480

American (AMR) AF: 0.137 AC: 4637 AN: 33952

Ashkenazi Jewish (ASJ) AF: 0.0655 AC: 1488 AN: 22732

East Asian (EAS) AF: 0.310 AC: 11050 AN: 35656

South Asian (SAS) AF: 0.164 AC: 12061 AN: 73678

European-Finnish (FIN) AF: 0.103 AC: 5026 AN: 48822

Middle Eastern (MID) AF: 0.0647 AC: 311 AN: 4810

European-Non Finnish (NFE) AF: 0.0782 AC: 73764 AN: 943592

Other (OTH) AF: 0.120 AC: 6338 AN: 52634

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

African (AFR) AF: 0.337 AC: 13997 AN: 41498

American (AMR) AF: 0.135 AC: 2069 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.315 AC: 1630 AN: 5172

South Asian (SAS) AF: 0.168 AC: 812 AN: 4822

European-Finnish (FIN) AF: 0.0968 AC: 1027 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0755 AC: 5137 AN: 68006

Other (OTH) AF: 0.133 AC: 281 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.64
PhyloP100		0.0050
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: rs2282001; hg19: chr9-35377772; COSMIC: COSV65934154;