rs139116481
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001136472.2(LITAF):c.330C>T(p.Asn110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,614,178 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00063 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00095 ( 6 hom. )
Consequence
LITAF
NM_001136472.2 synonymous
NM_001136472.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.807
Genes affected
LITAF (HGNC:16841): (lipopolysaccharide induced TNF factor) Lipopolysaccharide is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor-alpha (TNF-alpha) and other inflammatory mediators. This gene encodes lipopolysaccharide-induced TNF-alpha factor, which is a DNA-binding protein and can mediate the TNF-alpha expression by direct binding to the promoter region of the TNF-alpha gene. The transcription of this gene is induced by tumor suppressor p53 and has been implicated in the p53-induced apoptotic pathway. Mutations in this gene cause Charcot-Marie-Tooth disease type 1C (CMT1C) and may be involved in the carcinogenesis of extramammary Paget's disease (EMPD). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 16-11553580-G-A is Benign according to our data. Variant chr16-11553580-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 219573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-11553580-G-A is described in Lovd as [Benign]. Variant chr16-11553580-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.807 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00063 (96/152304) while in subpopulation EAS AF= 0.00173 (9/5190). AF 95% confidence interval is 0.000904. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 96 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LITAF | NM_001136472.2 | c.330C>T | p.Asn110= | synonymous_variant | 3/4 | ENST00000622633.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LITAF | ENST00000622633.5 | c.330C>T | p.Asn110= | synonymous_variant | 3/4 | 1 | NM_001136472.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000631 AC: 96AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000876 AC: 220AN: 251180Hom.: 3 AF XY: 0.000869 AC XY: 118AN XY: 135762
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GnomAD4 exome AF: 0.000947 AC: 1385AN: 1461874Hom.: 6 Cov.: 31 AF XY: 0.000960 AC XY: 698AN XY: 727238
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GnomAD4 genome AF: 0.000630 AC: 96AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000550 AC XY: 41AN XY: 74480
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Inherited Neuropathy Consortium | - | - - |
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease type 1C Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 29, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 14, 2020 | This variant is associated with the following publications: (PMID: 15776429, 19396477) - |
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