dbSNP rs813592: GCKR:c.429-38T>C (chr2-27499104-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001486.4(GCKR):c.429-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,301,156 control chromosomes in the GnomAD database, including 112,732 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18031 hom., cov: 32)

Exomes 𝑓: 0.40 ( 94701 hom. )

Consequence

GCKR
NM_001486.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.112

Publications

21 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-27499104-T-C is Benign according to our data. Variant chr2-27499104-T-C is described in ClinVar as Benign. ClinVar VariationId is 1275596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 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.429-38T>C		intron	N/A	NP_001477.2	A0A0C4DFN2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GCKR	ENST00000264717.7	TSL:1 MANE Select	c.429-38T>C	intron	N/A	ENSP00000264717.2	A0A0C4DFN2
GCKR	ENST00000472290.1	TSL:1	n.451-38T>C	intron	N/A
GCKR	ENST00000867122.1		c.429-38T>C	intron	N/A	ENSP00000537181.1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70708

AN:

151918

Hom.:

17988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.220

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.151

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.412

GnomAD2 exomes

AF:

0.417

AC:

104282

AN:

249880

AF XY:

0.407

show subpopulations

Gnomad AFR exome

AF:

0.679

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.151

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.397

AC:

456416

AN:

1149120

Hom.:

94701

Cov.:

AF XY:

0.395

AC XY:

231792

AN XY:

586844

show subpopulations

African (AFR)

AF:

0.681

AC:

18818

AN:

27648

American (AMR)

AF:

0.555

AC:

24572

AN:

44254

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8253

AN:

24132

East Asian (EAS)

AF:

0.131

AC:

5029

AN:

38300

South Asian (SAS)

AF:

0.419

AC:

33535

AN:

80022

European-Finnish (FIN)

AF:

0.433

AC:

23007

AN:

53188

Middle Eastern (MID)

AF:

0.357

AC:

1814

AN:

5086

European-Non Finnish (NFE)

AF:

0.389

AC:

321561

AN:

826476

Other (OTH)

AF:

0.396

AC:

19827

AN:

50014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

15334

30668

46002

61336

76670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9020

18040

27060

36080

45100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.466

AC:

70811

AN:

152036

Hom.:

18031

Cov.:

AF XY:

0.464

AC XY:

34500

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.671

AC:

27808

AN:

41442

American (AMR)

AF:

0.472

AC:

7209

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1178

AN:

3472

East Asian (EAS)

AF:

0.151

AC:

780

AN:

5170

South Asian (SAS)

AF:

0.427

AC:

2060

AN:

4820

European-Finnish (FIN)

AF:

0.429

AC:

4527

AN:

10564

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26062

AN:

67970

Other (OTH)

AF:

0.415

AC:

875

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1773

3546

5318

7091

8864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.407

Hom.:

4258

Bravo

AF:

0.476

Asia WGS

AF:

0.364

AC:

1264

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.8

(source)

DANN

Benign

0.70

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over