rs2284769

Positions:

• chr7-44182621-C-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+6288G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,106 control chromosomes in the GnomAD database, including 931 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 0.099 (931 hom., cov: 32)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100

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]

LOC105375257 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.45+6288G>C		intron_variant		ENST00000403799.8
LOC105375257	XR_927221.3	n.82-681C>G		intron_variant, non_coding_transcript_variant
GCK	NM_001354800.1	c.45+6288G>C		intron_variant
LOC105375257	XR_927222.3	n.759+472C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.45+6288G>C		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 15029 AN: 151988 Hom.: 930 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0988 AC: 15032 AN: 152106 Hom.: 931 Cov.: 32 AF XY: 0.101 AC XY: 7514 AN XY: 74334

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0766

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.115

Alfa AF: 0.109 Hom.: 127

Bravo AF: 0.0974

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.4
DANN	Benign	0.40

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: rs2284769; hg19: chr7-44222220;