9-35289547-G-A

Variant names:

• chr9-35289547-G-A
• rs10758303
• NM_001371189.2:c.527-6149G>A

Variant summary

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

The NM_001371189.2(UNC13B):​c.527-6149G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 151,984 control chromosomes in the GnomAD database, including 18,939 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 0.50 (18939 hom., cov: 32)
• Consequence: UNC13B NM_001371189.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	NM_001371189.2	MANE Select	c.527-6149G>A		intron	N/A	NP_001358118.1
	UNC13B	NM_001330653.3		c.527-6149G>A		intron	N/A	NP_001317582.1
	UNC13B	NM_001387551.1		c.527-1522G>A		intron	N/A	NP_001374480.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC13B	ENST00000635942.2	TSL:5 MANE Select	c.527-6149G>A		intron	N/A	ENSP00000490228.1
	UNC13B	ENST00000619578.4	TSL:1	c.527-6149G>A		intron	N/A	ENSP00000479261.1
	UNC13B	ENST00000378495.7	TSL:1	c.527-6149G>A		intron	N/A	ENSP00000367756.3

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75204 AN: 151866 Hom.: 18924 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.495 AC: 75233 AN: 151984 Hom.: 18939 Cov.: 32 AF XY: 0.495 AC XY: 36792 AN XY: 74272

African (AFR) AF: 0.444 AC: 18404 AN: 41462

American (AMR) AF: 0.446 AC: 6813 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1966 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2851 AN: 5168

South Asian (SAS) AF: 0.464 AC: 2234 AN: 4812

European-Finnish (FIN) AF: 0.508 AC: 5351 AN: 10532

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35781 AN: 67958

Other (OTH) AF: 0.506 AC: 1069 AN: 2112

Alfa AF: 0.514 Hom.: 68478

Bravo AF: 0.490

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.40
PhyloP100		-0.47
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: rs10758303; hg19: chr9-35289544; COSMIC: COSV65937997;