Variant chr2-27497495-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001486.4(GCKR):c.217-67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,565,922 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 8 hom. )

Consequence

GCKR
NM_001486.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.431

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 2-27497495-C-G is Benign according to our data. Variant chr2-27497495-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1218676.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00762 (1161/152298) while in subpopulation AFR AF= 0.0263 (1094/41552). AF 95% confidence interval is 0.025. There are 11 homozygotes in gnomad4. There are 521 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GCKR	NM_001486.4 linkuse as main transcript	c.217-67C>G	intron_variant	ENST00000264717.7
GCKR	XM_011532763.1 linkuse as main transcript	c.217-67C>G	intron_variant
GCKR	XR_001738699.1 linkuse as main transcript	n.283-67C>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GCKR	ENST00000264717.7 linkuse as main transcript	c.217-67C>G	intron_variant	1	NM_001486.4	P1
GCKR	ENST00000472290.1 linkuse as main transcript	n.239-67C>G	intron_variant, non_coding_transcript_variant	1
GCKR	ENST00000453813.1 linkuse as main transcript	c.133-67C>G	intron_variant	3
GCKR	ENST00000417872.5 linkuse as main transcript	n.274-67C>G	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1161

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00478

GnomAD4 exome

AF:

0.000738

AC:

1043

AN:

1413624

Hom.:

Cov.:

AF XY:

0.000636

AC XY:

449

AN XY:

706322

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000421

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00762

AC:

1161

AN:

152298

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

521

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0263

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00600

Hom.:

Bravo

AF:

0.00834

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

DANN

Benign

0.46

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