rs780092

Positions:

• chr2-27520287-A-G
• chr2-27520287-A-T

Variant summary

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

The ENST00000264717.7(GCKR):​c.1572+1350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,966 control chromosomes in the GnomAD database, including 2,717 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 0.18 (2717 hom., cov: 31)
• Consequence: GCKR ENST00000264717.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

Genes affected

GCKR (HGNC:4196): (glucokinase regulator) This gene encodes a protein belonging to the GCKR subfamily of the SIS (Sugar ISomerase) family of proteins. The gene product is a regulatory protein that inhibits glucokinase in liver and pancreatic islet cells by binding non-covalently to form an inactive complex with the enzyme. This gene is considered a susceptibility gene candidate for a form of maturity-onset diabetes of the young (MODY). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCKR	NM_001486.4	c.1572+1350A>G		intron_variant		ENST00000264717.7	NP_001477.2
GCKR	XM_017003796.2	c.1002+1350A>G		intron_variant			XP_016859285.1
GCKR	XM_017003797.2	c.1002+1350A>G		intron_variant			XP_016859286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.1572+1350A>G		intron_variant		1	NM_001486.4	ENSP00000264717	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27347 AN: 151846 Hom.: 2694 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.180 AC: 27419 AN: 151966 Hom.: 2717 Cov.: 31 AF XY: 0.183 AC XY: 13562 AN XY: 74270

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.154

Alfa AF: 0.156 Hom.: 4178

Bravo AF: 0.177

Asia WGS AF: 0.307 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.85

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: rs780092; hg19: chr2-27743154;