rs4923940

Variant names:

• chr15-42293176-T-A
• rs4923940
• NM_198141.3:c.512+259T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000318010.13(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 ENST00000318010.13 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000318010.13. 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
	GANC	NM_198141.3	MANE Select	c.512+259T>A		intron	N/A	NP_937784.2
	GANC	NM_001393928.1		c.512+259T>A		intron	N/A	NP_001380857.1
	GANC	NM_001393929.1		c.512+259T>A		intron	N/A	NP_001380858.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GANC	ENST00000318010.13	TSL:1 MANE Select	c.512+259T>A		intron	N/A	ENSP00000326227.8
	GANC	ENST00000566442.5	TSL:2	c.512+259T>A		intron	N/A	ENSP00000454747.1
	GANC	ENST00000567421.1	TSL:5	n.485+259T>A		intron	N/A

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

African (AFR) AF: 0.168 AC: 6983 AN: 41504

American (AMR) AF: 0.684 AC: 10455 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2710 AN: 3468

East Asian (EAS) AF: 0.840 AC: 4349 AN: 5180

South Asian (SAS) AF: 0.660 AC: 3188 AN: 4830

European-Finnish (FIN) AF: 0.868 AC: 9194 AN: 10588

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58775 AN: 68016

Other (OTH) AF: 0.688 AC: 1452 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.62
PhyloP100		-0.0090
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: rs4923940; hg19: chr15-42585374;