rs267606537
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_003977.4(AIP):c.140_163delGCACCGTGCTGGACGACAGCCGGG(p.Gly47_Arg54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AIP
NM_003977.4 disruptive_inframe_deletion
NM_003977.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.10
Genes affected
AIP (HGNC:358): (aryl hydrocarbon receptor interacting protein) The protein encoded by this gene is a receptor for aryl hydrocarbons and a ligand-activated transcription factor. The encoded protein is found in the cytoplasm as part of a multiprotein complex, but upon binding of ligand is transported to the nucleus. This protein can regulate the expression of many xenobiotic metabolizing enzymes. Also, the encoded protein can bind specifically to and inhibit the activity of hepatitis B virus. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_003977.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AIP | NM_003977.4 | c.140_163delGCACCGTGCTGGACGACAGCCGGG | p.Gly47_Arg54del | disruptive_inframe_deletion | 2/6 | ENST00000279146.8 | NP_003968.3 | |
AIP | NM_001302960.2 | c.140_163delGCACCGTGCTGGACGACAGCCGGG | p.Gly47_Arg54del | disruptive_inframe_deletion | 2/6 | NP_001289889.1 | ||
AIP | NM_001302959.2 | c.-38_-15delGCACCGTGCTGGACGACAGCCGGG | 5_prime_UTR_variant | 2/6 | NP_001289888.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AIP | ENST00000279146.8 | c.140_163delGCACCGTGCTGGACGACAGCCGGG | p.Gly47_Arg54del | disruptive_inframe_deletion | 2/6 | 1 | NM_003977.4 | ENSP00000279146.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251330Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461730Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727156
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 24, 2023 | This variant, c.140_163del, results in the deletion of 8 amino acid(s) of the AIP protein (p.Gly47_Arg54del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 41163). This variant has been observed in individual(s) with acromegaly (PMID: 22720333). This variant is present in population databases (rs267606537, gnomAD 0.0009%). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 20, 2024 | The c.140_163del24 variant (also known as p.G47_R54del) is located in coding exon 2 of the AIP gene. This variant results from an in-frame GCACCGTGCTGGACGACAGCCGGG deletion at nucleotide positions 140 to 163. This results in the in-frame deletion of eight amino acids (GTVLDDSR) at codons 47 to 54. This variant has been reported in several patients with pituitary adenomas (Daly AF et al. J Clin Endocrinol Metab, 2007 May;92:1891-6; Joshi K et al. Horm Res Paediatr, 2018 Jun;90:196-202) including one individual whose tumor demonstrated a deletion on chromosome 11 and, therefore, loss of wild type AIP (Gummadavelli A et al. J Clin Neurosci, 2020 Aug;78:420-422). This amino acid region is generally well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the available evidence, the clinical significance of this variant remains unclear. - |
Somatotroph adenoma Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at