7-44182405-A-T

Position:

• chr7-44182405-A-T

Variant summary

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

The ENST00000403799.8(GCK):​c.45+6504T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 151,562 control chromosomes in the GnomAD database, including 20,702 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 0.52 (20702 hom., cov: 32)
• Consequence: GCK ENST00000403799.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCK	NM_000162.5	c.45+6504T>A		intron_variant		ENST00000403799.8	NP_000153.1
LOC105375257	XR_927221.3	n.82-897A>T		intron_variant, non_coding_transcript_variant
GCK	NM_001354800.1	c.45+6504T>A		intron_variant			NP_001341729.1
LOC105375257	XR_927222.3	n.759+256A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCK	ENST00000403799.8	c.45+6504T>A		intron_variant		1	NM_000162.5	ENSP00000384247	P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78622 AN: 151442 Hom.: 20674 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.519 AC: 78695 AN: 151562 Hom.: 20702 Cov.: 32 AF XY: 0.523 AC XY: 38689 AN XY: 74026

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.505

Alfa AF: 0.541 Hom.: 2825

Bravo AF: 0.507

Asia WGS AF: 0.521 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.50

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: rs1076439; hg19: chr7-44222004;