chr19-41352912-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1_ModeratePM1PM2PP3_StrongPP5_Moderate
The NM_000660.7(TGFB1):c.133C>T(p.Arg45Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_000660.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGFB1 | NM_000660.7 | c.133C>T | p.Arg45Cys | missense_variant | 1/7 | ENST00000221930.6 | |
TGFB1 | XM_011527242.3 | c.133C>T | p.Arg45Cys | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGFB1 | ENST00000221930.6 | c.133C>T | p.Arg45Cys | missense_variant | 1/7 | 1 | NM_000660.7 | P1 | |
TMEM91 | ENST00000539627.5 | c.-30+1710G>A | intron_variant | 1 | |||||
TGFB1 | ENST00000600196.2 | c.133C>T | p.Arg45Cys | missense_variant | 1/6 | 5 | |||
TGFB1 | ENST00000677934.1 | c.133C>T | p.Arg45Cys | missense_variant | 1/5 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 7.11e-7 AC: 1AN: 1405514Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1AN XY: 694734
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inflammatory bowel disease, immunodeficiency, and encephalopathy Pathogenic:2
Likely pathogenic, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Feb 27, 2019 | This variant is interpreted as a Likely pathogenic for Inflammatory bowel disease, immunodeficiency, and encephalopathy, autosomal recessive. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 : Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3-Moderate : PS3 downgraded in strength to Moderate (PMID:29483653). PP1 : Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:29483653). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 04, 2018 | - - |
Encephalopathy;C4749850:Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | research | Klein lab, Ludwig-Maximilians-University | Jan 01, 2017 | Variant is associated with primary immunodeficiency, inflammatory bowel disease and encephalopathy. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at