2-211383683-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_005235.3(ERBB4):c.3859G>A(p.Glu1287Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. E1287D) has been classified as Uncertain significance.
Frequency
Consequence
NM_005235.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERBB4 | NM_005235.3 | c.3859G>A | p.Glu1287Lys | missense_variant | 28/28 | ENST00000342788.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERBB4 | ENST00000342788.9 | c.3859G>A | p.Glu1287Lys | missense_variant | 28/28 | 1 | NM_005235.3 | P4 | |
ERBB4 | ENST00000436443.5 | c.3811G>A | p.Glu1271Lys | missense_variant | 27/27 | 1 | A1 | ||
ERBB4 | ENST00000260943.11 | c.3781G>A | p.Glu1261Lys | missense_variant | 27/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251114Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135740
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727194
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74310
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 13, 2021 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals affected with ERBB4-related conditions. This sequence change replaces glutamic acid with lysine at codon 1287 of the ERBB4 protein (p.Glu1287Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs367568427, ExAC 0.003%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at