chr9-35343559-C-G

Variant names:

• chr9-35343559-C-G
• rs17296428
• NM_001371189.2:c.9415-23388C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371189.2(UNC13B):​c.9415-23388C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,100 control chromosomes in the GnomAD database, including 1,463 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 0.12 (1463 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.434
• Publications: 2 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 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.9415-23388C>G		intron	N/A	NP_001358118.1	A0A1B0GUS7
	UNC13B	NM_001371187.2		c.-234+1215C>G		intron	N/A	NP_001358116.1	A0A1B0GVW8
	UNC13B	NM_001387555.1		c.-234+1215C>G		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.9415-23388C>G		intron	N/A	ENSP00000490228.1	A0A1B0GUS7
	UNC13B	ENST00000619578.4	TSL:1	c.1168-23388C>G		intron	N/A	ENSP00000479261.1	O14795-2
	UNC13B	ENST00000378495.7	TSL:1	c.1168-23388C>G		intron	N/A	ENSP00000367756.3	O14795-1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18780 AN: 151980 Hom.: 1463 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.141

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

GnomAD4 genome AF: 0.123 AC: 18782 AN: 152100 Hom.: 1463 Cov.: 32 AF XY: 0.126 AC XY: 9353 AN XY: 74344

African (AFR) AF: 0.0343 AC: 1423 AN: 41508

American (AMR) AF: 0.150 AC: 2296 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3470

East Asian (EAS) AF: 0.154 AC: 798 AN: 5178

South Asian (SAS) AF: 0.103 AC: 496 AN: 4806

European-Finnish (FIN) AF: 0.167 AC: 1761 AN: 10554

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10959 AN: 67988

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.0637 Hom.: 72

Bravo AF: 0.119

Asia WGS AF: 0.157 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		0.43
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: rs17296428; hg19: chr9-35343556;