rs2908287

Positions:

• chr7-44191827-A-G
• chr7-44191827-A-T

Variant summary

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

The ENST00000476008.1(GCK):​n.480+5864T>C 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 0.776 in 152,056 control chromosomes in the GnomAD database, including 45,856 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 0.78 (45856 hom., cov: 31)
• Consequence: GCK ENST00000476008.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 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+5864T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117876 AN: 151936 Hom.: 45817 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.776 AC: 117974 AN: 152056 Hom.: 45856 Cov.: 31 AF XY: 0.778 AC XY: 57783 AN XY: 74318

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.763

Alfa AF: 0.675 Hom.: 1924

Bravo AF: 0.778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2908287; hg19: chr7-44231426;