chr2-27518370-T-C

Variant names:

• chr2-27518370-T-C
• rs780094
• NM_001486.4:c.1423-418T>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.1423-418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,110 control chromosomes in the GnomAD database, including 34,550 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 0.66 (34550 hom., cov: 32)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 843 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4	c.1423-418T>C		intron_variant	Intron 16 of 18	ENST00000264717.7	NP_001477.2
GCKR	XM_017003796.2	c.853-418T>C		intron_variant	Intron 11 of 13		XP_016859285.1
GCKR	XM_017003797.2	c.853-418T>C		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.1423-418T>C		intron_variant	Intron 16 of 18	1	NM_001486.4	ENSP00000264717.2

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100893 AN: 151992 Hom.: 34482 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.664 AC: 101032 AN: 152110 Hom.: 34550 Cov.: 32 AF XY: 0.663 AC XY: 49313 AN XY: 74346

African (AFR) AF: 0.825 AC: 34262 AN: 41510

American (AMR) AF: 0.618 AC: 9445 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2647 AN: 5174

South Asian (SAS) AF: 0.763 AC: 3685 AN: 4830

European-Finnish (FIN) AF: 0.632 AC: 6680 AN: 10566

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40673 AN: 67970

Other (OTH) AF: 0.601 AC: 1270 AN: 2112

Alfa AF: 0.611 Hom.: 136320

Bravo AF: 0.667

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		-0.18
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: rs780094; hg19: chr2-27741237;