NM_005235.3:c.3859G>A
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 (★).
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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERBB4 | ENST00000342788.9 | c.3859G>A | p.Glu1287Lys | missense_variant | Exon 28 of 28 | 1 | NM_005235.3 | ENSP00000342235.4 | ||
ERBB4 | ENST00000436443.5 | c.3811G>A | p.Glu1271Lys | missense_variant | Exon 27 of 27 | 1 | ENSP00000403204.1 | |||
ERBB4 | ENST00000260943.11 | c.3781G>A | p.Glu1261Lys | missense_variant | Exon 27 of 27 | 5 | ENSP00000260943.7 |
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
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 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"). This variant has not been reported in the literature in individuals affected with ERBB4-related conditions. This variant is present in population databases (rs367568427, ExAC 0.003%). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at