chr19-42248740-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_006494.4(ERF):c.1372C>T(p.Arg458Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,480 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. R458G) has been classified as Uncertain significance.
Frequency
Consequence
NM_006494.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERF | NM_006494.4 | c.1372C>T | p.Arg458Cys | missense_variant | 4/4 | ENST00000222329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERF | ENST00000222329.9 | c.1372C>T | p.Arg458Cys | missense_variant | 4/4 | 1 | NM_006494.4 | P1 | |
ERF | ENST00000440177.6 | c.1147C>T | p.Arg383Cys | missense_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248476Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134852
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461250Hom.: 0 Cov.: 33 AF XY: 0.0000426 AC XY: 31AN XY: 726910
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
TWIST1-related craniosynostosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2023 | 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 ERF protein function. This variant has not been reported in the literature in individuals affected with ERF-related conditions. This variant is present in population databases (rs766642440, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 458 of the ERF protein (p.Arg458Cys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at