Genetic Variant GANC:c.1644+154C>T (chr15-42329603-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198141.3(GANC):c.1644+154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 546,984 control chromosomes in the GnomAD database, including 2,329 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 0.10 ( 1142 hom., cov: 32)

Exomes 𝑓: 0.066 ( 1187 hom. )

Consequence

GANC
NM_198141.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.34

Publications

2 publications found

Variant links:

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]

GANC links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GANC	NM_198141.3	MANE Select	c.1644+154C>T	intron	N/A	NP_937784.2
GANC	NM_001393928.1		c.1644+154C>T	intron	N/A	NP_001380857.1
GANC	NM_001393929.1		c.1644+154C>T	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.1644+154C>T		intron	N/A	ENSP00000326227.8
	GANC	ENST00000568953.1	TSL:3	n.*99C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15655

AN:

152010

Hom.:

1134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.0554

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0983

Gnomad FIN

AF:

0.0303

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0533

Gnomad OTH

AF:

0.107

GnomAD4 exome

AF:

0.0657

AC:

25959

AN:

394856

Hom.:

1187

AF XY:

0.0664

AC XY:

13280

AN XY:

199962

show subpopulations

African (AFR)

AF:

0.173

AC:

1761

AN:

10150

American (AMR)

AF:

0.246

AC:

2585

AN:

10494

Ashkenazi Jewish (ASJ)

AF:

0.0516

AC:

559

AN:

10834

East Asian (EAS)

AF:

0.0716

AC:

1803

AN:

25172

South Asian (SAS)

AF:

0.113

AC:

1614

AN:

14282

European-Finnish (FIN)

AF:

0.0322

AC:

788

AN:

24498

Middle Eastern (MID)

AF:

0.0529

AC:

AN:

1626

European-Non Finnish (NFE)

AF:

0.0543

AC:

14993

AN:

276060

Other (OTH)

AF:

0.0814

AC:

1770

AN:

21740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1138

2275

3413

4550

5688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.103

AC:

15680

AN:

152128

Hom.:

1142

Cov.:

AF XY:

0.104

AC XY:

7713

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.177

AC:

7336

AN:

41450

American (AMR)

AF:

0.193

AC:

2944

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0554

AC:

192

AN:

3468

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5188

South Asian (SAS)

AF:

0.0980

AC:

473

AN:

4828

European-Finnish (FIN)

AF:

0.0303

AC:

321

AN:

10592

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0532

AC:

3620

AN:

68008

Other (OTH)

AF:

0.106

AC:

224

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

685

1370

2055

2740

3425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0295

Hom.:

Bravo

AF:

0.119

Asia WGS

AF:

0.115

AC:

401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.15

(source)

DANN

Benign

0.72

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over