chr7-44181982-A-C

Position:

• chr7-44181982-A-C

Variant summary

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

The NM_000162.5(GCK):​c.45+6927T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,070 control chromosomes in the GnomAD database, including 55,725 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 0.86 (55725 hom., cov: 30)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.45+6927T>G		intron_variant		ENST00000403799.8
LOC105375257	XR_927221.3	n.82-1320A>C		intron_variant, non_coding_transcript_variant
GCK	NM_001354800.1	c.45+6927T>G		intron_variant
LOC105375257	XR_927222.3	n.592A>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.45+6927T>G		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129975 AN: 151952 Hom.: 55681 Cov.: 30

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.842

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

GnomAD4 genome AF: 0.855 AC: 130075 AN: 152070 Hom.: 55725 Cov.: 30 AF XY: 0.860 AC XY: 63977 AN XY: 74350

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.854

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.842

Alfa AF: 0.838 Hom.: 69523

Bravo AF: 0.850

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.1
DANN	Benign	0.79

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: rs758988; hg19: chr7-44221581;