rs4879877

Variant names:

• chr9-35181294-G-A
• rs4879877
• NM_001371189.2:c.22+18989G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-35181294-G-A
• chr9-35181294-G-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.22+18989G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,106 control chromosomes in the GnomAD database, including 51,281 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 0.82 (51281 hom., cov: 31)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 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.22+18989G>A		intron	N/A	NP_001358118.1
	UNC13B	NM_001330653.3		c.22+18989G>A		intron	N/A	NP_001317582.1
	UNC13B	NM_001387551.1		c.22+18989G>A		intron	N/A	NP_001374480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.22+18989G>A		intron	N/A	ENSP00000490228.1
	UNC13B	ENST00000619578.4	TSL:1	c.22+18989G>A		intron	N/A	ENSP00000479261.1
	UNC13B	ENST00000378495.7	TSL:1	c.22+18989G>A		intron	N/A	ENSP00000367756.3

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124535 AN: 151988 Hom.: 51264 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.819

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.819 AC: 124594 AN: 152106 Hom.: 51281 Cov.: 31 AF XY: 0.819 AC XY: 60922 AN XY: 74358

African (AFR) AF: 0.775 AC: 32144 AN: 41470

American (AMR) AF: 0.745 AC: 11385 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2877 AN: 3468

East Asian (EAS) AF: 0.982 AC: 5089 AN: 5180

South Asian (SAS) AF: 0.844 AC: 4072 AN: 4822

European-Finnish (FIN) AF: 0.810 AC: 8579 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57638 AN: 67974

Other (OTH) AF: 0.821 AC: 1736 AN: 2114

Alfa AF: 0.840 Hom.: 70350

Bravo AF: 0.812

Asia WGS AF: 0.887 AC: 3084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.45
PhyloP100		-0.24
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: rs4879877; hg19: chr9-35181291;