9-35191716-C-T

Variant names:

• chr9-35191716-C-T
• rs3904435
• NM_001371189.2:c.22+29411C>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.22+29411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,164 control chromosomes in the GnomAD database, including 41,431 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 0.73 (41431 hom., cov: 33)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 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+29411C>T		intron	N/A	NP_001358118.1	A0A1B0GUS7
	UNC13B	NM_001330653.3		c.22+29411C>T		intron	N/A	NP_001317582.1	O14795-2
	UNC13B	NM_001387551.1		c.22+29411C>T		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+29411C>T		intron	N/A	ENSP00000490228.1	A0A1B0GUS7
	UNC13B	ENST00000619578.4	TSL:1	c.22+29411C>T		intron	N/A	ENSP00000479261.1	O14795-2
	UNC13B	ENST00000378495.7	TSL:1	c.22+29411C>T		intron	N/A	ENSP00000367756.3	O14795-1

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111366 AN: 152046 Hom.: 41417 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.732 AC: 111412 AN: 152164 Hom.: 41431 Cov.: 33 AF XY: 0.727 AC XY: 54092 AN XY: 74378

African (AFR) AF: 0.630 AC: 26137 AN: 41486

American (AMR) AF: 0.646 AC: 9880 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2731 AN: 3472

East Asian (EAS) AF: 0.682 AC: 3527 AN: 5168

South Asian (SAS) AF: 0.715 AC: 3455 AN: 4830

European-Finnish (FIN) AF: 0.728 AC: 7711 AN: 10590

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55344 AN: 68014

Other (OTH) AF: 0.745 AC: 1575 AN: 2114

Alfa AF: 0.774 Hom.: 64036

Bravo AF: 0.721

Asia WGS AF: 0.702 AC: 2438 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.7
DANN	Benign	0.32
PhyloP100		0.18
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3904435;

hg19: chr9-35191713;