NM_001486.4:c.1422+2334G>A

Variant names:

• chr2-27510585-G-A
• rs4425043
• NM_001486.4:c.1422+2334G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001486.4(GCKR):​c.1422+2334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,928 control chromosomes in the GnomAD database, including 11,793 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 0.39 (11793 hom., cov: 32)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 13 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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.1422+2334G>A		intron_variant	Intron 16 of 18	ENST00000264717.7	NP_001477.2
GCKR	XM_017003796.2	c.852+2334G>A		intron_variant	Intron 11 of 13		XP_016859285.1
GCKR	XM_017003797.2	c.852+2334G>A		intron_variant	Intron 10 of 12		XP_016859286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7	c.1422+2334G>A		intron_variant	Intron 16 of 18	1	NM_001486.4	ENSP00000264717.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58981 AN: 151808 Hom.: 11770 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.389 AC: 59037 AN: 151928 Hom.: 11793 Cov.: 32 AF XY: 0.389 AC XY: 28893 AN XY: 74264

African (AFR) AF: 0.406 AC: 16809 AN: 41378

American (AMR) AF: 0.442 AC: 6743 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.159 AC: 823 AN: 5170

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4511 AN: 10524

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25752 AN: 67978

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.347 Hom.: 3116

Bravo AF: 0.388

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.4
DANN	Benign	0.70
PhyloP100		0.28
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: rs4425043; hg19: chr2-27733452;