7-44186230-A-G

Position:

• chr7-44186230-A-G

Variant summary

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

The NM_000162.5(GCK):​c.45+2679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,274 control chromosomes in the GnomAD database, including 349 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 0.065 (349 hom., cov: 33)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCK	NM_000162.5	c.45+2679T>C		intron_variant		ENST00000403799.8	NP_000153.1
GCK	NM_001354800.1	c.45+2679T>C		intron_variant			NP_001341729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCK	ENST00000403799.8	c.45+2679T>C		intron_variant		1	NM_000162.5	ENSP00000384247	P1

Frequencies

GnomAD3 genomes AF: 0.0654 AC: 9955 AN: 152156 Hom.: 347 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.0697

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0654 AC: 9964 AN: 152274 Hom.: 349 Cov.: 33 AF XY: 0.0651 AC XY: 4848 AN XY: 74458

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.0697

Gnomad4 NFE AF: 0.0718

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0380 Hom.: 37

Bravo AF: 0.0637

Asia WGS AF: 0.0730 AC: 255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.49
DANN	Benign	0.51

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: rs34807880; hg19: chr7-44225829;