rs150425546
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001134831.2(AHI1):c.1791C>T(p.Ile597=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,607,948 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0030 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00042 ( 5 hom. )
Consequence
AHI1
NM_001134831.2 synonymous
NM_001134831.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.658
Genes affected
AHI1 (HGNC:21575): (Abelson helper integration site 1) This gene is apparently required for both cerebellar and cortical development in humans. This gene mutations cause specific forms of Joubert syndrome-related disorders. Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
Variant 6-135442703-G-A is Benign according to our data. Variant chr6-135442703-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-135442703-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.658 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.1791C>T | p.Ile597= | synonymous_variant | 14/29 | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.1791C>T | p.Ile597= | synonymous_variant | 14/29 | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00290 AC: 442AN: 152154Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 185AN: 243498Hom.: 1 AF XY: 0.000530 AC XY: 70AN XY: 132136
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GnomAD4 exome AF: 0.000416 AC: 606AN: 1455676Hom.: 5 Cov.: 30 AF XY: 0.000344 AC XY: 249AN XY: 723832
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
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, Academic Medical Center | - | - - |
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 | Eurofins Ntd Llc (ga) | May 19, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 07, 2018 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | AHI1: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2018 | - - |
Joubert syndrome 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at