rs814295

Positions:

• chr2-27520348-A-G

Variant summary

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

The NM_001486.4(GCKR):​c.1572+1411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,080 control chromosomes in the GnomAD database, including 2,782 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 (2782 hom., cov: 31)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCKR	NM_001486.4	c.1572+1411A>G		intron_variant		ENST00000264717.7
GCKR	XM_017003796.2	c.1002+1411A>G		intron_variant
GCKR	XM_017003797.2	c.1002+1411A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCKR	ENST00000264717.7	c.1572+1411A>G		intron_variant		1	NM_001486.4	P1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27717 AN: 151962 Hom.: 2759 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.183 AC: 27789 AN: 152080 Hom.: 2782 Cov.: 31 AF XY: 0.185 AC XY: 13758 AN XY: 74340

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.157

Alfa AF: 0.175 Hom.: 480

Bravo AF: 0.179

Asia WGS AF: 0.308 AC: 1068 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	3.1
DANN	Benign	0.41

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: rs814295; hg19: chr2-27743215;