rs814295

Variant names:

• chr2-27520348-A-G
• rs814295
• NM_001486.4:c.1572+1411A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.1572+1411A>G		intron_variant	Intron 17 of 18	ENST00000264717.7	NP_001477.2
GCKR	XM_017003796.2	c.1002+1411A>G		intron_variant	Intron 12 of 13		XP_016859285.1
GCKR	XM_017003797.2	c.1002+1411A>G		intron_variant	Intron 11 of 12		XP_016859286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.1572+1411A>G		intron_variant	Intron 17 of 18	1	NM_001486.4	ENSP00000264717.2

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

African (AFR) AF: 0.231 AC: 9592 AN: 41456

American (AMR) AF: 0.119 AC: 1818 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5164

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4818

European-Finnish (FIN) AF: 0.167 AC: 1767 AN: 10588

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.157 AC: 10702 AN: 67990

Other (OTH) AF: 0.157 AC: 331 AN: 2114

Alfa AF: 0.172 Hom.: 3253

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
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs814295; hg19: chr2-27743215;