rs150355046
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001270508.2(TNFAIP3):c.2231G>A(p.Gly744Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000618 in 1,613,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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_001270508.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNFAIP3 | NM_001270508.2 | c.2231G>A | p.Gly744Asp | missense_variant | 9/9 | ENST00000612899.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNFAIP3 | ENST00000612899.5 | c.2231G>A | p.Gly744Asp | missense_variant | 9/9 | 5 | NM_001270508.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000388 AC: 59AN: 151974Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000459 AC: 115AN: 250718Hom.: 0 AF XY: 0.000479 AC XY: 65AN XY: 135704
GnomAD4 exome AF: 0.000642 AC: 939AN: 1461642Hom.: 1 Cov.: 31 AF XY: 0.000611 AC XY: 444AN XY: 727126
GnomAD4 genome ? AF: 0.000388 AC: 59AN: 151974Hom.: 0 Cov.: 32 AF XY: 0.000404 AC XY: 30AN XY: 74206
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2022 | Reported in an individual with axial spondyloarthritis, but detailed clinical and segregation information were not provided (Liu et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28791018, 24728327) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | TNFAIP3: BP4, BS1 - |
Autoinflammatory syndrome, familial, Behcet-like 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 14, 2023 | The TNFAIP3 c.2231G>A; p.Gly744Asp variant (rs150355046), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 135348). This variant is found in the non-Finnish European population with an allele frequency of 0.07% (90/128,668 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.023). While the high population frequency suggests that this is likely a benign variant, given the lack of clinical and functional data, the significance of this variant is uncertain at this time. - |
TNFAIP3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 16, 2022 | 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). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at