rs1476891

Variant names:

• chr7-44190369-G-A
• rs1476891
• ENST00000476008.1:n.480+7322C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-44190369-G-A
• chr7-44190369-G-C
• chr7-44190369-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000476008.1(GCK):​n.480+7322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.697 in 152,090 control chromosomes in the GnomAD database, including 37,061 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 0.70 (37061 hom., cov: 33)
• Consequence: GCK ENST00000476008.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• hyperinsulinism due to glucokinase deficiency

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• maturity-onset diabetes of the young type 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• monogenic diabetes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• permanent neonatal diabetes mellitus 1

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• transient neonatal diabetes mellitus

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• permanent neonatal diabetes mellitus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000476008.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCK	ENST00000476008.1	TSL:5	n.480+7322C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.697 AC: 105962 AN: 151970 Hom.: 37024 Cov.: 33

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.697 AC: 106052 AN: 152090 Hom.: 37061 Cov.: 33 AF XY: 0.699 AC XY: 52009 AN XY: 74352

African (AFR) AF: 0.735 AC: 30497 AN: 41490

American (AMR) AF: 0.702 AC: 10734 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2312 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3837 AN: 5174

South Asian (SAS) AF: 0.708 AC: 3414 AN: 4820

European-Finnish (FIN) AF: 0.685 AC: 7240 AN: 10570

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45842 AN: 67970

Other (OTH) AF: 0.687 AC: 1452 AN: 2114

Alfa AF: 0.689 Hom.: 10226

Bravo AF: 0.699

Asia WGS AF: 0.715 AC: 2487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.40
PhyloP100		-0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1476891; hg19: chr7-44229968;