chr5-157244427-G-T
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005546.4(ITK):c.1398G>T(p.Val466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00629 in 1,614,044 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0058 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0063 ( 121 hom. )
Consequence
ITK
NM_005546.4 synonymous
NM_005546.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.08
Genes affected
ITK (HGNC:6171): (IL2 inducible T cell kinase) This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 5-157244427-G-T is Benign according to our data. Variant chr5-157244427-G-T is described in ClinVar as [Benign]. Clinvar id is 540360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-157244427-G-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.09 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00577 (879/152320) while in subpopulation SAS AF= 0.0246 (119/4830). AF 95% confidence interval is 0.021. There are 6 homozygotes in gnomad4. There are 449 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITK | NM_005546.4 | c.1398G>T | p.Val466= | synonymous_variant | 13/17 | ENST00000422843.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITK | ENST00000422843.8 | c.1398G>T | p.Val466= | synonymous_variant | 13/17 | 1 | NM_005546.4 | P1 | |
ITK | ENST00000519749.1 | n.468G>T | non_coding_transcript_exon_variant | 3/6 | 1 | ||||
ITK | ENST00000519402.5 | n.2983G>T | non_coding_transcript_exon_variant | 12/16 | 2 | ||||
ITK | ENST00000696962.1 | c.*175G>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/16 |
Frequencies
GnomAD3 genomes ? AF: 0.00576 AC: 877AN: 152202Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00880 AC: 2210AN: 251180Hom.: 39 AF XY: 0.0103 AC XY: 1400AN XY: 135738
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GnomAD4 exome AF: 0.00634 AC: 9272AN: 1461724Hom.: 121 Cov.: 32 AF XY: 0.00718 AC XY: 5219AN XY: 727174
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lymphoproliferative syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 13, 2018 | - - |
Autoinflammatory syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Oct 18, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at