rs3736762
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_031483.7(ITCH):c.1210+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,193,640 control chromosomes in the GnomAD database, including 143,032 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.45 ( 15737 hom., cov: 31)
Exomes 𝑓: 0.49 ( 127295 hom. )
Consequence
ITCH
NM_031483.7 intron
NM_031483.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.01
Genes affected
ITCH (HGNC:13890): (itchy E3 ubiquitin protein ligase) This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation. The encoded protein plays a role in multiple cellular processes including erythroid and lymphoid cell differentiation and the regulation of immune responses. Mutations in this gene are a cause of syndromic multisystem autoimmune disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 20-34449531-C-T is Benign according to our data. Variant chr20-34449531-C-T is described in ClinVar as [Benign]. Clinvar id is 2628156.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITCH | NM_031483.7 | c.1210+51C>T | intron_variant | ENST00000374864.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITCH | ENST00000374864.10 | c.1210+51C>T | intron_variant | 1 | NM_031483.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.447 AC: 67888AN: 151720Hom.: 15730 Cov.: 31
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GnomAD3 exomes AF: 0.458 AC: 109681AN: 239352Hom.: 26412 AF XY: 0.468 AC XY: 60409AN XY: 129050
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GnomAD4 exome AF: 0.488 AC: 507880AN: 1041802Hom.: 127295 Cov.: 14 AF XY: 0.489 AC XY: 261955AN XY: 535980
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GnomAD4 genome AF: 0.447 AC: 67928AN: 151838Hom.: 15737 Cov.: 31 AF XY: 0.450 AC XY: 33408AN XY: 74186
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 55% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at