rs780093

Positions:

• chr2-27519736-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCKR	NM_001486.4	c.1572+799T>C		intron_variant		ENST00000264717.7
GCKR	XM_017003796.2	c.1002+799T>C		intron_variant
GCKR	XM_017003797.2	c.1002+799T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCKR	ENST00000264717.7	c.1572+799T>C		intron_variant		1	NM_001486.4	P1

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

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.608

Alfa AF: 0.593 Hom.: 37746

Bravo AF: 0.677

Asia WGS AF: 0.693 AC: 2409 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	0.91
DANN	Benign	0.47

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: rs780093; hg19: chr2-27742603;