rs4923940

Positions:

• chr15-42293176-T-A
• chr15-42293176-T-C
• chr15-42293176-T-G

Variant summary

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

The NM_198141.3(GANC):​c.512+259T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,186 control chromosomes in the GnomAD database, including 38,698 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 0.65 (38698 hom., cov: 33)
• Consequence: GANC NM_198141.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GANC	NM_198141.3	c.512+259T>A		intron_variant		ENST00000318010.13	NP_937784.2
GANC	NM_001301409.2	c.512+259T>A		intron_variant			NP_001288338.1
GANC	NM_001393928.1	c.512+259T>A		intron_variant			NP_001380857.1
GANC	NM_001393929.1	c.512+259T>A		intron_variant			NP_001380858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GANC	ENST00000318010.13	c.512+259T>A		intron_variant		1	NM_198141.3	ENSP00000326227	P1
GANC	ENST00000566442.5	c.512+259T>A		intron_variant		2		ENSP00000454747
GANC	ENST00000567421.1	n.485+259T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98249 AN: 152068 Hom.: 38707 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.645 AC: 98231 AN: 152186 Hom.: 38698 Cov.: 33 AF XY: 0.648 AC XY: 48196 AN XY: 74420

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.684

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.688

Alfa AF: 0.744 Hom.: 5856

Bravo AF: 0.614

Asia WGS AF: 0.711 AC: 2472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.62

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: rs4923940; hg19: chr15-42585374;