rs2971679

Positions:

• chr7-44151710-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.363+561G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,242 control chromosomes in the GnomAD database, including 4,055 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 0.21 (4055 hom., cov: 34)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.363+561G>A		intron_variant		ENST00000403799.8
GCK	NM_001354800.1	c.363+561G>A		intron_variant
GCK	NM_033507.3	c.366+561G>A		intron_variant
GCK	NM_033508.3	c.360+561G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.363+561G>A		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32581 AN: 152124 Hom.: 4047 Cov.: 34

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.214 AC: 32620 AN: 152242 Hom.: 4055 Cov.: 34 AF XY: 0.214 AC XY: 15965 AN XY: 74442

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.180

Alfa AF: 0.191 Hom.: 418

Bravo AF: 0.217

Asia WGS AF: 0.186 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.75

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: rs2971679; hg19: chr7-44191309;