rs113317693
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001134831.2(AHI1):c.1152-11T>G variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.0025 in 1,393,940 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 44 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 41 hom. )
Consequence
AHI1
NM_001134831.2 splice_polypyrimidine_tract, intron
NM_001134831.2 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.01728
2
Clinical Significance
Conservation
PhyloP100: 5.37
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 6-135455937-A-C is Benign according to our data. Variant chr6-135455937-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 235332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1850/152296) while in subpopulation AFR AF= 0.0424 (1763/41546). AF 95% confidence interval is 0.0408. There are 44 homozygotes in gnomad4. There are 858 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 44 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHI1 | NM_001134831.2 | c.1152-11T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000265602.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHI1 | ENST00000265602.11 | c.1152-11T>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001134831.2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0121 AC: 1842AN: 152178Hom.: 44 Cov.: 32
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GnomAD3 exomes AF: 0.00416 AC: 516AN: 123930Hom.: 15 AF XY: 0.00322 AC XY: 209AN XY: 64838
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GnomAD4 exome AF: 0.00131 AC: 1629AN: 1241644Hom.: 41 Cov.: 28 AF XY: 0.00115 AC XY: 692AN XY: 599870
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GnomAD4 genome ? AF: 0.0121 AC: 1850AN: 152296Hom.: 44 Cov.: 32 AF XY: 0.0115 AC XY: 858AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Joubert syndrome 3 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 16, 2021 | - - |
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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 10, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Familial aplasia of the vermis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
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