Variant 2-27496896-C-T 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.-9C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000986 in 1,611,866 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 7 hom. )

Consequence

GCKR
NM_001486.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

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=-0.8).

BP6

Variant 2-27496896-C-T is Benign according to our data. Variant chr2-27496896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194950.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00498 (758/152224) while in subpopulation AFR AF= 0.0174 (721/41540). AF 95% confidence interval is 0.0163. There are 3 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
GCKR	NM_001486.4 linkuse as main transcript	c.-9C>T	5_prime_UTR_variant	1/19	ENST00000264717.7	NP_001477.2
GCKR	XM_011532763.1 linkuse as main transcript	c.-9C>T	5_prime_UTR_variant	1/13		XP_011531065.1
GCKR	XR_001738699.1 linkuse as main transcript	n.58C>T	non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
GCKR	ENST00000264717.7 linkuse as main transcript	c.-9C>T	5_prime_UTR_variant	1/19	1	NM_001486.4	ENSP00000264717	P1
GCKR	ENST00000472290.1 linkuse as main transcript	n.14C>T	non_coding_transcript_exon_variant	1/11	1
GCKR	ENST00000417872.5 linkuse as main transcript	n.49C>T	non_coding_transcript_exon_variant	1/7	4

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

756

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00146

AC:

366

AN:

251450

Hom.:

AF XY:

0.00113

AC XY:

154

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000570

AC:

832

AN:

1459642

Hom.:

Cov.:

AF XY:

0.000512

AC XY:

372

AN XY:

726260

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000862

GnomAD4 genome

AF:

0.00498

AC:

758

AN:

152224

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

370

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00258

Hom.:

Bravo

AF:

0.00558

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

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

Nov 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.6

DANN

Benign

0.59

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