rs1799884
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1
The ENST00000476008.1(GCK):n.480+8222G>A 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 0.163 in 199,940 control chromosomes in the GnomAD database, including 2,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.17 ( 2204 hom., cov: 33)
Exomes 𝑓: 0.14 ( 579 hom. )
Consequence
GCK
ENST00000476008.1 intron, non_coding_transcript
ENST00000476008.1 intron, non_coding_transcript
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.555
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=-0.25).
BP6
?
Variant 7-44189469-C-T is Benign according to our data. Variant chr7-44189469-C-T is described in ClinVar as [Benign]. Clinvar id is 1258742.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCK | NM_000162.5 | upstream_gene_variant | ENST00000403799.8 | ||||
GCK | NM_001354800.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCK | ENST00000403799.8 | upstream_gene_variant | 1 | NM_000162.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.170 AC: 25879AN: 152068Hom.: 2200 Cov.: 33
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GnomAD4 exome AF: 0.141 AC: 6757AN: 47754Hom.: 579 Cov.: 0 AF XY: 0.141 AC XY: 3486AN XY: 24720
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GnomAD4 genome ? AF: 0.170 AC: 25890AN: 152186Hom.: 2204 Cov.: 33 AF XY: 0.167 AC XY: 12464AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 28, 2018 | This variant is associated with the following publications: (PMID: 24520939, 8603762, 19018513, 16186409, 15677518, 15173029, 21697023) - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at