NM_001486.4:c.869+74C>G

Variant names:

• chr2-27505910-C-G
• rs2293572
• NM_001486.4:c.869+74C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001486.4(GCKR):​c.869+74C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 866,018 control chromosomes in the GnomAD database, including 65,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11585 hom., cov: 30)
  • Exomes 𝑓: 0.38 (54321 hom.)
• Consequence: GCKR NM_001486.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.421
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-27505910-C-G is Benign according to our data. Variant chr2-27505910-C-G is described in ClinVar as Benign. ClinVar VariationId is 1249652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.433 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCKR	NM_001486.4	MANE Select	c.869+74C>G		intron	N/A	NP_001477.2	A0A0C4DFN2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCKR	ENST00000264717.7	TSL:1 MANE Select	c.869+74C>G		intron	N/A	ENSP00000264717.2	A0A0C4DFN2
	GCKR	ENST00000472290.1	TSL:1	n.891+74C>G		intron	N/A
	GCKR	ENST00000867122.1		c.869+74C>G		intron	N/A	ENSP00000537181.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58415 AN: 151714 Hom.: 11563 Cov.: 30

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.357

GnomAD4 exome AF: 0.379 AC: 270941 AN: 714186 Hom.: 54321 AF XY: 0.380 AC XY: 145683 AN XY: 383534

African (AFR) AF: 0.383 AC: 7365 AN: 19254

American (AMR) AF: 0.537 AC: 23347 AN: 43488

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 7057 AN: 21232

East Asian (EAS) AF: 0.144 AC: 5170 AN: 35840

South Asian (SAS) AF: 0.435 AC: 30838 AN: 70852

European-Finnish (FIN) AF: 0.429 AC: 20711 AN: 48226

Middle Eastern (MID) AF: 0.340 AC: 1416 AN: 4168

European-Non Finnish (NFE) AF: 0.372 AC: 161828 AN: 435454

Other (OTH) AF: 0.370 AC: 13209 AN: 35672

GnomAD4 genome AF: 0.385 AC: 58463 AN: 151832 Hom.: 11585 Cov.: 30 AF XY: 0.386 AC XY: 28609 AN XY: 74184

African (AFR) AF: 0.393 AC: 16260 AN: 41416

American (AMR) AF: 0.442 AC: 6743 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3468

East Asian (EAS) AF: 0.156 AC: 806 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2157 AN: 4804

European-Finnish (FIN) AF: 0.429 AC: 4522 AN: 10530

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

European-Non Finnish (NFE) AF: 0.379 AC: 25743 AN: 67878

Other (OTH) AF: 0.361 AC: 763 AN: 2112

Alfa AF: 0.375 Hom.: 1333

Bravo AF: 0.384

Asia WGS AF: 0.347 AC: 1204 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.64
PhyloP100		-0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2293572; hg19: chr2-27728777; COSMIC: COSV53111772; COSMIC: COSV53111772;