Variant rs2268574 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000162.5(GCK):c.679+38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 1,592,566 control chromosomes in the GnomAD database, including 207,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 25486 hom., cov: 32)

Exomes 𝑓: 0.50 ( 181745 hom. )

Consequence

GCK
NM_000162.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.77

Variant links:

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]

GCK links:

LOC105375258 (HGNC:):

LOC105375258 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 7-44149722-A-G is Benign according to our data. Variant chr7-44149722-A-G is described in ClinVar as [Benign]. Clinvar id is 673534.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-44149722-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCK	NM_000162.5 linkuse as main transcript	c.679+38T>C		intron_variant		ENST00000403799.8	NP_000153.1
LOC105375258	XR_927223.3 linkuse as main transcript	n.253A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCK	ENST00000403799.8 linkuse as main transcript	c.679+38T>C		intron_variant		1	NM_000162.5	ENSP00000384247	P1	P35557-1

Frequencies

GnomAD3 genomes

AF:

0.570

AC:

86483

AN:

151798

Hom.:

25462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.729

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.567

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.531

AC:

132823

AN:

250270

Hom.:

36046

AF XY:

0.518

AC XY:

70099

AN XY:

135390

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.595

Gnomad ASJ exome

AF:

0.495

Gnomad EAS exome

AF:

0.661

Gnomad SAS exome

AF:

0.435

Gnomad FIN exome

AF:

0.497

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.499

AC:

718976

AN:

1440652

Hom.:

181745

Cov.:

AF XY:

0.496

AC XY:

356115

AN XY:

717960

show subpopulations

Gnomad4 AFR exome

AF:

0.735

Gnomad4 AMR exome

AF:

0.593

Gnomad4 ASJ exome

AF:

0.498

Gnomad4 EAS exome

AF:

0.631

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.488

Gnomad4 OTH exome

AF:

0.504

GnomAD4 genome

AF:

0.570

AC:

86554

AN:

151914

Hom.:

25486

Cov.:

AF XY:

0.569

AC XY:

42208

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.729

Gnomad4 AMR

AF:

0.567

Gnomad4 ASJ

AF:

0.503

Gnomad4 EAS

AF:

0.630

Gnomad4 SAS

AF:

0.436

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.536

Hom.:

4572

Bravo

AF:

0.585

Asia WGS

AF:

0.524

AC:

1822

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.19

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over