2-27508073-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001486.4(GCKR):āc.1337T>Cā(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 0.617 in 1,610,248 control chromosomes in the GnomAD database, including 312,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (ā ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.
Frequency
Consequence
NM_001486.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCKR | NM_001486.4 | c.1337T>C | p.Leu446Pro | missense_variant, splice_region_variant | 15/19 | ENST00000264717.7 | |
GCKR | XM_017003796.2 | c.767T>C | p.Leu256Pro | missense_variant, splice_region_variant | 10/14 | ||
GCKR | XM_017003797.2 | c.767T>C | p.Leu256Pro | missense_variant, splice_region_variant | 9/13 | ||
GCKR | XR_001738699.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCKR | ENST00000264717.7 | c.1337T>C | p.Leu446Pro | missense_variant, splice_region_variant | 15/19 | 1 | NM_001486.4 | P1 | |
GCKR | ENST00000411584.1 | c.440T>C | p.Leu147Pro | missense_variant, splice_region_variant | 5/7 | 3 | |||
GCKR | ENST00000478147.1 | n.534T>C | splice_region_variant, non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.670 AC: 101762AN: 151894Hom.: 35360 Cov.: 31
GnomAD3 exomes AF: 0.633 AC: 159003AN: 251160Hom.: 51710 AF XY: 0.631 AC XY: 85704AN XY: 135752
GnomAD4 exome AF: 0.612 AC: 892119AN: 1458234Hom.: 277034 Cov.: 34 AF XY: 0.613 AC XY: 445037AN XY: 725598
GnomAD4 genome ? AF: 0.670 AC: 101903AN: 152014Hom.: 35431 Cov.: 31 AF XY: 0.669 AC XY: 49718AN XY: 74306
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2018 | This 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 provided | literature only | OMIM | Feb 01, 2010 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at