chr2-221426112-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_004438.5(EPHA4):c.2877C>A(p.Ile959=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,882 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 Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
EPHA4
NM_004438.5 synonymous
NM_004438.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.220
Genes affected
EPHA4 (HGNC:3388): (EPH receptor A4) This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 2-221426112-G-T is Benign according to our data. Variant chr2-221426112-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2983521.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.22 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPHA4 | NM_004438.5 | c.2877C>A | p.Ile959= | synonymous_variant | 17/18 | ENST00000281821.7 | |
EPHA4 | NM_001304536.2 | c.2877C>A | p.Ile959= | synonymous_variant | 18/19 | ||
EPHA4 | NM_001304537.2 | c.2724C>A | p.Ile908= | synonymous_variant | 16/17 | ||
EPHA4 | NM_001363748.2 | c.*56C>A | 3_prime_UTR_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPHA4 | ENST00000281821.7 | c.2877C>A | p.Ile959= | synonymous_variant | 17/18 | 1 | NM_004438.5 | P1 | |
EPHA4 | ENST00000409854.5 | c.*56C>A | 3_prime_UTR_variant | 17/17 | 1 | ||||
EPHA4 | ENST00000409938.5 | c.2877C>A | p.Ile959= | synonymous_variant | 18/18 | 2 | P1 | ||
EPHA4 | ENST00000424339.1 | c.*181C>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251454Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727244
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at