Genetic Variant GCKR:c.869+74C>G (chr2-27505910-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.421

Variant links:

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]

GCKR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GCKR	NM_001486.4 link	c.869+74C>G		intron_variant	Intron 10 of 18	ENST00000264717.7	NP_001477.2	Q14397A0A0C4DFN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GCKR	ENST00000264717.7 link	c.869+74C>G		intron_variant	Intron 10 of 18	1	NM_001486.4	ENSP00000264717.2		A0A0C4DFN2
GCKR	ENST00000472290.1 link	n.891+74C>G		intron_variant	Intron 10 of 10	1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58415

AN:

151714

Hom.:

11563

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.537

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.144

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.372

Gnomad4 OTH exome

AF:

0.370

GnomAD4 genome

AF:

0.385

AC:

58463

AN:

151832

Hom.:

11585

Cov.:

AF XY:

0.386

AC XY:

28609

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.449

Gnomad4 FIN

AF:

0.429

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.375

Hom.:

1333

Bravo

AF:

0.384

Asia WGS

AF:

0.347

AC:

1204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.3

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over