chr19-42248740-G-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_006494.4(ERF):c.1372C>G(p.Arg458Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R458C) 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>G | p.Arg458Gly | missense_variant | 4/4 | ENST00000222329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERF | ENST00000222329.9 | c.1372C>G | p.Arg458Gly | missense_variant | 4/4 | 1 | NM_006494.4 | P1 | |
ERF | ENST00000440177.6 | c.1147C>G | p.Arg383Gly | missense_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248476Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134852
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461254Hom.: 0 Cov.: 33 AF XY: 0.0000330 AC XY: 24AN XY: 726912
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74374
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2021 | The c.1372C>G (p.R458G) alteration is located in exon 4 (coding exon 4) of the ERF gene. This alteration results from a C to G substitution at nucleotide position 1372, causing the arginine (R) at amino acid position 458 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
TWIST1-related craniosynostosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with ERF-related conditions. This variant is present in population databases (rs766642440, ExAC 0.01%). This sequence change replaces arginine with glycine at codon 458 of the ERF protein (p.Arg458Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at