rs13239289

Positions:

• chr7-44187089-C-G
• chr7-44187089-C-T

Variant summary

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

The NM_000162.5(GCK):​c.45+1820G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0545 in 152,334 control chromosomes in the GnomAD database, including 292 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 (292 hom., cov: 33)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.45+1820G>C		intron_variant		ENST00000403799.8
GCK	NM_001354800.1	c.45+1820G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.45+1820G>C		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8296 AN: 152216 Hom.: 291 Cov.: 33

Gnomad AFR AF: 0.0170

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0695

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0642

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

GnomAD4 genome AF: 0.0545 AC: 8299 AN: 152334 Hom.: 292 Cov.: 33 AF XY: 0.0543 AC XY: 4044 AN XY: 74490

Gnomad4 AFR AF: 0.0170

Gnomad4 AMR AF: 0.0470

Gnomad4 ASJ AF: 0.0640

Gnomad4 EAS AF: 0.0854

Gnomad4 SAS AF: 0.0691

Gnomad4 FIN AF: 0.0695

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0271 Hom.: 21

Bravo AF: 0.0514

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13239289; hg19: chr7-44226688;