rs12534623

Positions:

• chr7-44152604-A-G
• chr7-44152604-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000162.5(GCK):​c.209-179T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 151,862 control chromosomes in the GnomAD database, including 8,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (8757 hom., cov: 31)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.794

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-44152604-A-G is Benign according to our data. Variant chr7-44152604-A-G is described in ClinVar as [Benign]. Clinvar id is 1235046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.209-179T>C		intron_variant		ENST00000403799.8
GCK	NM_001354800.1	c.209-179T>C		intron_variant
GCK	NM_033507.3	c.212-179T>C		intron_variant
GCK	NM_033508.3	c.206-179T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.209-179T>C		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51482 AN: 151744 Hom.: 8757 Cov.: 31

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.339 AC: 51494 AN: 151862 Hom.: 8757 Cov.: 31 AF XY: 0.340 AC XY: 25274 AN XY: 74232

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.357

Alfa AF: 0.353 Hom.: 1980

Bravo AF: 0.343

Asia WGS AF: 0.319 AC: 1113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.41

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: rs12534623; hg19: chr7-44192203;