rs3735935
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000503.6(EYA1):c.1476-21G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,610,736 control chromosomes in the GnomAD database, including 91,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.32 ( 8629 hom., cov: 33)
Exomes 𝑓: 0.32 ( 83186 hom. )
Consequence
EYA1
NM_000503.6 intron
NM_000503.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.593
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=-0.84).
BP6
?
Variant 8-71215529-C-A is Benign according to our data. Variant chr8-71215529-C-A is described in ClinVar as [Benign]. Clinvar id is 1253275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-71215529-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYA1 | NM_000503.6 | c.1476-21G>T | intron_variant | ENST00000340726.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYA1 | ENST00000340726.8 | c.1476-21G>T | intron_variant | 1 | NM_000503.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.320 AC: 48658AN: 151902Hom.: 8613 Cov.: 33
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GnomAD3 exomes AF: 0.378 AC: 94834AN: 250698Hom.: 20585 AF XY: 0.374 AC XY: 50644AN XY: 135582
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GnomAD4 exome AF: 0.323 AC: 471592AN: 1458716Hom.: 83186 Cov.: 33 AF XY: 0.325 AC XY: 236222AN XY: 725890
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GnomAD4 genome ? AF: 0.320 AC: 48712AN: 152020Hom.: 8629 Cov.: 33 AF XY: 0.329 AC XY: 24434AN XY: 74318
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Branchiootic syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Branchiootorenal syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Otofaciocervical syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
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