rs41288017
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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.2505G>A(p.Arg835=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,602,692 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0038 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0048 ( 26 hom. )
Consequence
AHI1
NM_001134831.2 synonymous
NM_001134831.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.54
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=-0.28).
BP6
?
Variant 6-135428747-C-T is Benign according to our data. Variant chr6-135428747-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 194870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-135428747-C-T is described in Lovd as [Benign]. Variant chr6-135428747-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.54 with no splicing effect.
BS2
?
High Homozygotes in GnomAdExome4 at 26 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.2505G>A | p.Arg835= | synonymous_variant | 19/29 | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.2505G>A | p.Arg835= | synonymous_variant | 19/29 | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00379 AC: 575AN: 151726Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00385 AC: 907AN: 235472Hom.: 1 AF XY: 0.00405 AC XY: 516AN XY: 127380
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GnomAD4 exome AF: 0.00481 AC: 6977AN: 1450848Hom.: 26 Cov.: 30 AF XY: 0.00490 AC XY: 3532AN XY: 720906
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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:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 05, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | AHI1: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 18, 2019 | This variant is associated with the following publications: (PMID: 18782849, 16453322) - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Joubert syndrome 3 Benign:1
Likely 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 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 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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