chr2-221426114-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_004438.5(EPHA4):c.2875A>G(p.Ile959Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I959I) has been classified as Likely benign.
Frequency
Consequence
NM_004438.5 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 |
---|---|---|---|---|---|---|---|
EPHA4 | NM_004438.5 | c.2875A>G | p.Ile959Val | missense_variant | 17/18 | ENST00000281821.7 | |
EPHA4 | NM_001304536.2 | c.2875A>G | p.Ile959Val | missense_variant | 18/19 | ||
EPHA4 | NM_001304537.2 | c.2722A>G | p.Ile908Val | missense_variant | 16/17 | ||
EPHA4 | NM_001363748.2 | c.*54A>G | 3_prime_UTR_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHA4 | ENST00000281821.7 | c.2875A>G | p.Ile959Val | missense_variant | 17/18 | 1 | NM_004438.5 | P1 | |
EPHA4 | ENST00000409854.5 | c.*54A>G | 3_prime_UTR_variant | 17/17 | 1 | ||||
EPHA4 | ENST00000409938.5 | c.2875A>G | p.Ile959Val | missense_variant | 18/18 | 2 | P1 | ||
EPHA4 | ENST00000424339.1 | c.*179A>G | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251454Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135898
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727246
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 13, 2023 | This variant has not been reported in the literature in individuals affected with EPHA4-related conditions. 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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant is present in population databases (rs747243818, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 959 of the EPHA4 protein (p.Ile959Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at