1-160290586-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BS1_Supporting
The NM_004371.4(COPA):c.3521G>A(p.Arg1174Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1174W) has been classified as Benign.
Frequency
Consequence
NM_004371.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COPA | NM_004371.4 | c.3521G>A | p.Arg1174Gln | missense_variant | 32/33 | ENST00000241704.8 | |
LOC107985219 | XR_001738265.2 | n.537-671C>T | intron_variant, non_coding_transcript_variant | ||||
COPA | NM_001098398.2 | c.3548G>A | p.Arg1183Gln | missense_variant | 32/33 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COPA | ENST00000241704.8 | c.3521G>A | p.Arg1174Gln | missense_variant | 32/33 | 1 | NM_004371.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251460Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727244
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
ClinVar
Submissions by phenotype
Autoimmune interstitial lung disease-arthritis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | This variant is present in population databases (rs772329332, gnomAD 0.002%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COPA protein function. ClinVar contains an entry for this variant (Variation ID: 1384412). This variant has not been reported in the literature in individuals affected with COPA-related conditions. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1174 of the COPA protein (p.Arg1174Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at