rs4607517

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025): 0P and 4B. B1_Strong

The ENST00000849947.1(ENSG00000310458):n.67-1515G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.145 (AC=22,053) in the gnomAD database across 152,240 control chromosomes, including 1,706 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.178. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1706 hom., cov: 33)

Consequence

ENSG00000310458
ENST00000849947.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182

Publications

217 publications found

Variant links:

Genes affected

GCK (HGNC:4195): (glucokinase) This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]

GCK Gene-Disease associations (from GenCC):

hyperinsulinemic hypoglycemia, familial, 3
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia
maturity-onset diabetes of the young type 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
monogenic diabetes
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
diabetes mellitus, noninsulin-dependent
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
type 2 diabetes mellitus
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
permanent neonatal diabetes mellitus 1
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
transient neonatal diabetes mellitus
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
permanent neonatal diabetes mellitus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GCK links:

ENSG00000310458 (HGNC:):

ENSG00000310458 links:

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new If you want to explore the variant's impact on the transcript ENST00000849947.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.178 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000849947.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GCK	ENST00000476008.1	TSL:5	n.480+1622C>T	intron	N/A
ENSG00000310458	ENST00000849947.1		n.67-1515G>A	intron	N/A
ENSG00000310458	ENST00000849948.1		n.65-1576G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22053

AN:

152122

Hom.:

1705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0857

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.171

Gnomad OTH

AF:

0.176

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

GnomAD4 genome

AF:

0.145

AC:

22053

AN:

152240

Hom.:

1706

Cov.:

AF XY:

0.143

AC XY:

10642

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0857

AC:

3562

AN:

41550

American (AMR)

AF:

0.183

AC:

2806

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

593

AN:

3468

East Asian (EAS)

AF:

0.188

AC:

973

AN:

5182

South Asian (SAS)

AF:

0.139

AC:

668

AN:

4822

European-Finnish (FIN)

AF:

0.109

AC:

1151

AN:

10602

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11618

AN:

68006

Other (OTH)

AF:

0.174

AC:

367

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

964

1929

2893

3858

4822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.166

Hom.:

10487

Bravo

AF:

0.151

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.215

AC:

26414

AN:

122748

Turkish Variome

AF:

0.173

AC:

267

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.206

AC:

1842

AN:

8960

Hom.:

189

ABraOM SABE-WGS-1171

AF:

0.187

AC:

438

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over