rs730497

Variant names:

• chr7-44184122-G-A
• rs730497
• NM_000162.5:c.45+4787C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-44184122-G-A
• chr7-44184122-G-C
• chr7-44184122-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+4787C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,140 control chromosomes in the GnomAD database, including 2,278 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 0.17 (2278 hom., cov: 33)
• Consequence: GCK NM_000162.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCK	NM_000162.5	c.45+4787C>T		intron_variant	Intron 1 of 9	ENST00000403799.8	NP_000153.1
GCK	NM_001354800.1	c.45+4787C>T		intron_variant	Intron 1 of 10		NP_001341729.1
LOC105375257	XR_927221.3	n.379G>A		non_coding_transcript_exon_variant	Exon 3 of 3
LOC105375257	XR_927222.3	n.1057G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCK	ENST00000403799.8	c.45+4787C>T		intron_variant	Intron 1 of 9	1	NM_000162.5	ENSP00000384247.3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26288 AN: 152022 Hom.: 2275 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.173 AC: 26298 AN: 152140 Hom.: 2278 Cov.: 33 AF XY: 0.170 AC XY: 12640 AN XY: 74382

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.204

Alfa AF: 0.169 Hom.: 4105

Bravo AF: 0.184

Asia WGS AF: 0.134 AC: 467 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	1.8
DANN	Benign	0.53

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: rs730497; hg19: chr7-44223721;