12-52949307-G-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_000224.3(KRT18):āc.134G>Cā(p.Arg45Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000177 in 1,610,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. R45R) has been classified as Likely benign.
Frequency
Genomes: š 0.00018 ( 0 hom., cov: 40)
Exomes š: 0.00018 ( 0 hom. )
Consequence
KRT18
NM_000224.3 missense
NM_000224.3 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 5.05
Genes affected
KRT18 (HGNC:6430): (keratin 18) KRT18 encodes the type I intermediate filament chain keratin 18. Keratin 18, together with its filament partner keratin 8, are perhaps the most commonly found members of the intermediate filament gene family. They are expressed in single layer epithelial tissues of the body. Mutations in this gene have been linked to cryptogenic cirrhosis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]
KRT8 (HGNC:6446): (keratin 8) This gene is a member of the type II keratin family clustered on the long arm of chromosome 12. Type I and type II keratins heteropolymerize to form intermediate-sized filaments in the cytoplasm of epithelial cells. The product of this gene typically dimerizes with keratin 18 to form an intermediate filament in simple single-layered epithelial cells. This protein plays a role in maintaining cellular structural integrity and also functions in signal transduction and cellular differentiation. Mutations in this gene cause cryptogenic cirrhosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM1
In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity K1C18_HUMAN
BS2
High AC in GnomAd4 at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRT18 | NM_000224.3 | c.134G>C | p.Arg45Pro | missense_variant | 1/7 | ENST00000388835.4 | |
KRT18 | NM_199187.2 | c.134G>C | p.Arg45Pro | missense_variant | 2/8 | ||
KRT8 | NM_001256293.2 | c.-47+408C>G | intron_variant | ||||
KRT8 | NR_045962.2 | n.405+149C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRT18 | ENST00000388835.4 | c.134G>C | p.Arg45Pro | missense_variant | 1/7 | 1 | NM_000224.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152274Hom.: 0 Cov.: 40
GnomAD3 genomes
AF:
AC:
27
AN:
152274
Hom.:
Cov.:
40
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000107 AC: 26AN: 243312Hom.: 0 AF XY: 0.000113 AC XY: 15AN XY: 133138
GnomAD3 exomes
AF:
AC:
26
AN:
243312
Hom.:
AF XY:
AC XY:
15
AN XY:
133138
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000177 AC: 258AN: 1458088Hom.: 0 Cov.: 36 AF XY: 0.000174 AC XY: 126AN XY: 725338
GnomAD4 exome
AF:
AC:
258
AN:
1458088
Hom.:
Cov.:
36
AF XY:
AC XY:
126
AN XY:
725338
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000177 AC: 27AN: 152274Hom.: 0 Cov.: 40 AF XY: 0.000148 AC XY: 11AN XY: 74392
GnomAD4 genome
AF:
AC:
27
AN:
152274
Hom.:
Cov.:
40
AF XY:
AC XY:
11
AN XY:
74392
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
ExAC
AF:
AC:
10
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
Hepatitis C virus, susceptibility to Other:1
not provided, no classification provided | literature only | STRNAD Lab, University Hospital of Ulm | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MVP
MPC
0.78
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at