rs12903690

Positions:

• chr15-42323107-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198141.3(GANC):​c.1293+1087A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,214 control chromosomes in the GnomAD database, including 2,534 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 0.15 (2534 hom., cov: 33)
• Consequence: GANC NM_198141.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310

Genes affected

GANC (HGNC:4139): (glucosidase alpha, neutral C) Glycosyl hydrolase enzymes hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. This gene encodes a member of glycosyl hydrolases family 31. This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. This is a key enzyme in glycogen metabolism and its gene localizes to a chromosomal region (15q15) that is associated with susceptibility to diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GANC	NM_198141.3	c.1293+1087A>G		intron_variant		ENST00000318010.13	NP_937784.2
GANC	NM_001393928.1	c.1293+1087A>G		intron_variant			NP_001380857.1
GANC	NM_001393929.1	c.1293+1087A>G		intron_variant			NP_001380858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GANC	ENST00000318010.13	c.1293+1087A>G		intron_variant		1	NM_198141.3	ENSP00000326227	P1
GANC	ENST00000567421.1	n.1266+1087A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23548 AN: 152096 Hom.: 2533 Cov.: 33

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.155 AC: 23546 AN: 152214 Hom.: 2534 Cov.: 33 AF XY: 0.153 AC XY: 11406 AN XY: 74432

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0573

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.155

Alfa AF: 0.202 Hom.: 5120

Bravo AF: 0.140

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs12903690; hg19: chr15-42615305;