rs117149407
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000503.6(EYA1):c.1699-3C>T variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0159 in 1,609,482 control chromosomes in the GnomAD database, including 269 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 17 hom., cov: 33)
Exomes 𝑓: 0.016 ( 252 hom. )
Consequence
EYA1
NM_000503.6 splice_region, splice_polypyrimidine_tract, intron
NM_000503.6 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.002517
2
Clinical Significance
Conservation
PhyloP100: 4.84
Genes affected
EYA1 (HGNC:3519): (EYA transcriptional coactivator and phosphatase 1) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as a transcriptional activator. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 8-71199423-G-A is Benign according to our data. Variant chr8-71199423-G-A is described in ClinVar as [Benign]. Clinvar id is 48105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-71199423-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0117 (1779/152352) while in subpopulation AMR AF= 0.0216 (331/15306). AF 95% confidence interval is 0.0197. There are 17 homozygotes in gnomad4. There are 848 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1779 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYA1 | NM_000503.6 | c.1699-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000340726.8 | |||
LOC105375894 | XR_007060958.1 | n.206+78G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYA1 | ENST00000340726.8 | c.1699-3C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000503.6 | P4 | |||
ENST00000521685.5 | n.476+78G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0117 AC: 1781AN: 152234Hom.: 17 Cov.: 33
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GnomAD3 exomes AF: 0.0151 AC: 3721AN: 246102Hom.: 51 AF XY: 0.0148 AC XY: 1974AN XY: 133268
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GnomAD4 exome AF: 0.0163 AC: 23811AN: 1457130Hom.: 252 Cov.: 31 AF XY: 0.0163 AC XY: 11791AN XY: 724954
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GnomAD4 genome ? AF: 0.0117 AC: 1779AN: 152352Hom.: 17 Cov.: 33 AF XY: 0.0114 AC XY: 848AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 14, 2012 | 1699-3C>T in Intron 16 of EYA1: This variant is not expected to have clinical si gnificance because it has been identified in 1.6% (114/7020) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs117149407). - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 18, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Branchiootic syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Melnick-Fraser syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Otofaciocervical syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at