rs34780996

Positions:

• chr7-44183696-G-A
• chr7-44183696-G-C
• chr7-44183696-G-T

Variant summary

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

The NM_000162.5(GCK):​c.45+5213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 152,234 control chromosomes in the GnomAD database, including 285 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 0.055 (285 hom., cov: 32)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCK	NM_000162.5	c.45+5213C>T		intron_variant		ENST00000403799.8
LOC105375257	XR_927221.3	n.240+236G>A		intron_variant, non_coding_transcript_variant
GCK	NM_001354800.1	c.45+5213C>T		intron_variant
LOC105375257	XR_927222.3	n.918+236G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCK	ENST00000403799.8	c.45+5213C>T		intron_variant		1	NM_000162.5	P1

Frequencies

GnomAD3 genomes AF: 0.0547 AC: 8325 AN: 152116 Hom.: 284 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.0688

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.0646

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

GnomAD4 genome AF: 0.0547 AC: 8328 AN: 152234 Hom.: 285 Cov.: 32 AF XY: 0.0546 AC XY: 4062 AN XY: 74440

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.0855

Gnomad4 SAS AF: 0.0688

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0715

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0191 Hom.: 17

Bravo AF: 0.0517

Asia WGS AF: 0.0710 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.44

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: rs34780996; hg19: chr7-44223295;