rs925615
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_014336.5(AIPL1):c.466-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,613,450 control chromosomes in the GnomAD database, including 4,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.065 ( 358 hom., cov: 32)
Exomes 𝑓: 0.078 ( 4619 hom. )
Consequence
AIPL1
NM_014336.5 intron
NM_014336.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.140
Genes affected
AIPL1 (HGNC:359): (aryl hydrocarbon receptor interacting protein like 1) Leber congenital amaurosis (LCA) is the most severe inherited retinopathy with the earliest age of onset and accounts for at least 5% of all inherited retinal diseases. Affected individuals are diagnosed at birth or in the first few months of life with nystagmus, severely impaired vision or blindness and an abnormal or flat electroretinogram. The photoreceptor/pineal-expressed gene, AIPL1, encoding aryl-hydrocarbon interacting protein-like 1, is located within the LCA4 candidate region. The encoded protein contains three tetratricopeptide motifs, consistent with chaperone or nuclear transport activity. Mutations in this gene may cause approximately 20% of recessive LCA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 17-6427083-A-G is Benign according to our data. Variant chr17-6427083-A-G is described in ClinVar as [Benign]. Clinvar id is 1245637.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-6427083-A-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIPL1 | NM_014336.5 | c.466-26T>C | intron_variant | ENST00000381129.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIPL1 | ENST00000381129.8 | c.466-26T>C | intron_variant | 1 | NM_014336.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0652 AC: 9917AN: 152112Hom.: 358 Cov.: 32
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GnomAD3 exomes AF: 0.0628 AC: 15760AN: 250826Hom.: 586 AF XY: 0.0638 AC XY: 8645AN XY: 135586
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GnomAD4 exome AF: 0.0775 AC: 113274AN: 1461220Hom.: 4619 Cov.: 36 AF XY: 0.0767 AC XY: 55784AN XY: 726908
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GnomAD4 genome ? AF: 0.0652 AC: 9922AN: 152230Hom.: 358 Cov.: 32 AF XY: 0.0635 AC XY: 4729AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
BranchPoint Hunter
?
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