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GeneBe

rs1260326

Variant summary

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

The NM_001486.4(GCKR):c.1337T>C(p.Leu446Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151894 control chromosomes in the gnomAD Genomes database, including 35360 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 35360 hom., cov: 31)
Exomes 𝑓: 0.63 ( 51710 hom. )

Consequence

GCKR
NM_001486.4 missense, splice_region

Scores

1
16
Splicing: ADA: 0.000004368
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 0.0750

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=1.074255E-6).
BP6
?
Variant 2-27508073-T-C is Benign according to our data. Variant chr2-27508073-T-C is described in ClinVar as [Benign]. Clinvar id is 8751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GCKRNM_001486.4 linkuse as main transcriptc.1337T>C p.Leu446Pro missense_variant, splice_region_variant 15/19 ENST00000264717.7
GCKRXM_017003796.2 linkuse as main transcriptc.767T>C p.Leu256Pro missense_variant, splice_region_variant 10/14
GCKRXM_017003797.2 linkuse as main transcriptc.767T>C p.Leu256Pro missense_variant, splice_region_variant 9/13
GCKRXR_001738699.1 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GCKRENST00000264717.7 linkuse as main transcriptc.1337T>C p.Leu446Pro missense_variant, splice_region_variant 15/191 NM_001486.4 P1
GCKRENST00000411584.1 linkuse as main transcriptc.440T>C p.Leu147Pro missense_variant, splice_region_variant 5/73
GCKRENST00000478147.1 linkuse as main transcriptn.534T>C splice_region_variant, non_coding_transcript_exon_variant 2/35

Frequencies

GnomAD3 genomes
AF:
0.670
AC:
101762
AN:
151894
Hom.:
35360
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.858
Gnomad AMI
AF:
0.708
Gnomad AMR
AF:
0.626
Gnomad ASJ
AF:
0.459
Gnomad EAS
AF:
0.501
Gnomad SAS
AF:
0.757
Gnomad FIN
AF:
0.638
Gnomad MID
AF:
0.490
Gnomad NFE
AF:
0.590
Gnomad OTH
AF:
0.611
GnomAD3 exomes
AF:
0.633
AC:
159003
AN:
251160
Hom.:
51710
AF XY:
0.631
AC XY:
85704
AN XY:
135752
show subpopulations
Gnomad AFR exome
AF:
0.868
Gnomad AMR exome
AF:
0.666
Gnomad ASJ exome
AF:
0.467
Gnomad EAS exome
AF:
0.511
Gnomad SAS exome
AF:
0.758
Gnomad FIN exome
AF:
0.643
Gnomad NFE exome
AF:
0.590
Gnomad OTH exome
AF:
0.600
GnomAD4 exome
AF:
0.612
AC:
892119
AN:
1458234
Hom.:
277034
AF XY:
0.613
AC XY:
445037
AN XY:
725598
show subpopulations
Gnomad4 AFR exome
AF:
0.863
Gnomad4 AMR exome
AF:
0.665
Gnomad4 ASJ exome
AF:
0.467
Gnomad4 EAS exome
AF:
0.468
Gnomad4 SAS exome
AF:
0.753
Gnomad4 FIN exome
AF:
0.646
Gnomad4 NFE exome
AF:
0.599
Gnomad4 OTH exome
AF:
0.611
Alfa
AF:
0.591
Hom.:
66863
Bravo
AF:
0.674
TwinsUK
AF:
0.600
AC:
2226
ALSPAC
AF:
0.594
AC:
2290
ESP6500AA
AF:
0.857
AC:
3776
ESP6500EA
AF:
0.583
AC:
5015
ExAC
AF:
0.642
AC:
77990
Asia WGS
AF:
0.695
AC:
2412
AN:
3478
EpiCase
AF:
0.552
EpiControl
AF:
0.553

ClinVar

Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeNov 04, 2022- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 12, 2018This variant is associated with the following publications: (PMID: 33588820, 28082259, 24918535, 22001757, 31118516, 30297969, 30315176, 30420299, 29632382, 29083407, 27516387, 27798624, 23586973, 28385800, 27346689, 26174136, 26043229, 26551672, 27398621, 28008009, 18556336, 23383164, 23894584, 21674002, 21423719, 22182842, 21525158, 19526250, 19643913, 24879641, 22038520, 18678614, 22958899) -
Fasting plasma glucose level quantitative trait locus 5 Other:1
association, no assertion criteria providedliterature onlyOMIMFeb 01, 2010- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.035
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
13
Dann
Benign
0.040
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.29
Eigen_PC
Benign
0.031
FATHMM_MKL
Benign
0.018
N
LIST_S2
Benign
0.24
T
MetaRNN
Benign
0.0000011
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
0.27
P;P
PrimateAI
Benign
0.48
T
PROVEAN
Benign
2.4
N
REVEL
Benign
0.080
Sift
Benign
1.0
T
Sift4G
Benign
0.75
T
Vest4
0.034
MPC
0.087
ClinPred
0.0021
T
GERP RS
3.0
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0000044
dbscSNV1_RF
Benign
0.0040
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.

Other links and lift over

dbSNP: rs1260326; hg19: chr2-27730940; COSMIC: COSV53108202; COSMIC: COSV53108202; API