rs144415484
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004100.5(EYA4):c.979G>A(p.Asp327Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000238 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D327H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004100.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYA4 | NM_004100.5 | c.979G>A | p.Asp327Asn | missense_variant | 12/20 | ENST00000355286.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYA4 | ENST00000355286.12 | c.979G>A | p.Asp327Asn | missense_variant | 12/20 | 1 | NM_004100.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152048Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000496 AC: 124AN: 250092Hom.: 0 AF XY: 0.000473 AC XY: 64AN XY: 135258
GnomAD4 exome AF: 0.000223 AC: 326AN: 1461592Hom.: 0 Cov.: 31 AF XY: 0.000208 AC XY: 151AN XY: 727128
GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000578 AC XY: 43AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 08, 2020 | This variant is associated with the following publications: (PMID: 28831623) - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | EYA4: BS1 - |
EYA4-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 03, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2015 | p.Asp327Asn in exon 12 of EYA4: This variant is not expected to have clinical si gnificance because it has been identified in 0.33% (22/6610) of Finnish chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs144415484). - |
Dilated cardiomyopathy 1J Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at