chr2-211383681-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005235.3(ERBB4):c.3861G>T(p.Glu1287Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERBB4 | ENST00000342788.9 | c.3861G>T | p.Glu1287Asp | missense_variant | Exon 28 of 28 | 1 | NM_005235.3 | ENSP00000342235.4 | ||
ERBB4 | ENST00000436443.5 | c.3813G>T | p.Glu1271Asp | missense_variant | Exon 27 of 27 | 1 | ENSP00000403204.1 | |||
ERBB4 | ENST00000260943.11 | c.3783G>T | p.Glu1261Asp | missense_variant | Exon 27 of 27 | 5 | ENSP00000260943.7 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251134Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135740
GnomAD4 exome AF: 0.0000978 AC: 143AN: 1461784Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 727194
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152260Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 1287 of the ERBB4 protein (p.Glu1287Asp). This variant is present in population databases (rs749222561, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ERBB4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1980190). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at