rs3757838

chr7-44191711-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+5980T>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 0.0545 in 152,288 control chromosomes in the GnomAD database, including 288 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 0.054 (288 hom., cov: 33)
• Consequence: GCK ENST00000476008.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0787 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+5980T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8293 AN: 152168 Hom.: 287 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0693

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0545 AC: 8296 AN: 152288 Hom.: 288 Cov.: 33 AF XY: 0.0542 AC XY: 4038 AN XY: 74464

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.0853

Gnomad4 SAS AF: 0.0691

Gnomad4 FIN AF: 0.0693

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0592 Hom.: 37

Bravo AF: 0.0514

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	12
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3757838; hg19: chr7-44231310;