rs2041547

Positions:

• chr7-44161285-T-C
• chr7-44161285-T-G

Variant summary

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

The NM_000162.5(GCK):​c.46-7822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,092 control chromosomes in the GnomAD database, including 29,291 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 0.61 (29291 hom., cov: 33)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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 = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.46-7822A>G		intron_variant		ENST00000403799.8
GCK	NM_001354800.1	c.46-7822A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.46-7822A>G		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92384 AN: 151974 Hom.: 29258 Cov.: 33

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.608 AC: 92462 AN: 152092 Hom.: 29291 Cov.: 33 AF XY: 0.608 AC XY: 45176 AN XY: 74344

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.587

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.585

Alfa AF: 0.567 Hom.: 6619

Bravo AF: 0.623

Asia WGS AF: 0.524 AC: 1822 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	3.1
DANN	Benign	0.48

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: rs2041547; hg19: chr7-44200884;