NM_001486.4:c.1572+799T>C

Variant names:

• chr2-27519736-T-C
• rs780093
• NM_001486.4:c.1572+799T>C

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+799T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,104 control chromosomes in the GnomAD database, including 35,743 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 0.67 (35743 hom., cov: 32)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 224 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 (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001486.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCKR	NM_001486.4	MANE Select	c.1572+799T>C		intron	N/A	NP_001477.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCKR	ENST00000264717.7	TSL:1 MANE Select	c.1572+799T>C		intron	N/A	ENSP00000264717.2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102328 AN: 151986 Hom.: 35675 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.674 AC: 102467 AN: 152104 Hom.: 35743 Cov.: 32 AF XY: 0.672 AC XY: 49984 AN XY: 74360

African (AFR) AF: 0.857 AC: 35559 AN: 41514

American (AMR) AF: 0.622 AC: 9505 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1599 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2622 AN: 5166

South Asian (SAS) AF: 0.765 AC: 3694 AN: 4826

European-Finnish (FIN) AF: 0.637 AC: 6726 AN: 10566

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40687 AN: 67970

Other (OTH) AF: 0.608 AC: 1284 AN: 2112

Alfa AF: 0.618 Hom.: 103361

Bravo AF: 0.677

Asia WGS AF: 0.693 AC: 2409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.47
PhyloP100		-0.085
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: rs780093; hg19: chr2-27742603;