rs1476891

Positions:

• chr7-44190369-G-A
• chr7-44190369-G-C
• chr7-44190369-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000476008.1(GCK):​n.480+7322C>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 0.697 in 152,090 control chromosomes in the GnomAD database, including 37,061 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 0.70 (37061 hom., cov: 33)
• Consequence: GCK ENST00000476008.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 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
GCK	ENST00000476008.1	n.480+7322C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105962 AN: 151970 Hom.: 37024 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.697 AC: 106052 AN: 152090 Hom.: 37061 Cov.: 33 AF XY: 0.699 AC XY: 52009 AN XY: 74352

Gnomad4 AFR AF: 0.735

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.708

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.687

Alfa AF: 0.688 Hom.: 8898

Bravo AF: 0.699

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1476891; hg19: chr7-44229968;