rs149625278
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2
The NM_031483.7(ITCH):c.467G>A(p.Cys156Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,612,954 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_031483.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITCH | NM_031483.7 | c.467G>A | p.Cys156Tyr | missense_variant | 6/25 | ENST00000374864.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITCH | ENST00000374864.10 | c.467G>A | p.Cys156Tyr | missense_variant | 6/25 | 1 | NM_031483.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000919 AC: 231AN: 251338Hom.: 1 AF XY: 0.00121 AC XY: 165AN XY: 135852
GnomAD4 exome AF: 0.000474 AC: 692AN: 1460704Hom.: 5 Cov.: 29 AF XY: 0.000652 AC XY: 474AN XY: 726778
GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74440
ClinVar
Submissions by phenotype
Syndromic multisystem autoimmune disease due to ITCH deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
ITCH-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 26, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at