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GeneBe

rs4607517

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000476008.1(GCK):n.480+1622C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,240 control chromosomes in the GnomAD database, including 1,706 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 0.14 ( 1706 hom., cov: 33)

Consequence

GCK
ENST00000476008.1 intron, non_coding_transcript

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCKENST00000476008.1 linkuse as main transcriptn.480+1622C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.145
AC:
22053
AN:
152122
Hom.:
1705
Cov.:
33
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.:
33
AF XY:
0.143
AC XY:
10642
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0857
Gnomad4 AMR
AF:
0.183
Gnomad4 ASJ
AF:
0.171
Gnomad4 EAS
AF:
0.188
Gnomad4 SAS
AF:
0.139
Gnomad4 FIN
AF:
0.109
Gnomad4 NFE
AF:
0.171
Gnomad4 OTH
AF:
0.174
Alfa
AF:
0.170
Hom.:
5214
Bravo
AF:
0.151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
Cadd
Benign
11
Dann
Benign
0.88

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4607517; hg19: chr7-44235668; API