rs267606537

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

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2O:1

Conservation

PhyloP100: 2.10
Variant links:
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]

Genome browser will be placed here

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
AIPNM_003977.4 linkuse as main transcriptc.140_163delGCACCGTGCTGGACGACAGCCGGG p.Gly47_Arg54del disruptive_inframe_deletion 2/6 ENST00000279146.8 NP_003968.3 O00170
AIPNM_001302960.2 linkuse as main transcriptc.140_163delGCACCGTGCTGGACGACAGCCGGG p.Gly47_Arg54del disruptive_inframe_deletion 2/6 NP_001289889.1 O00170A0A804HJ38
AIPNM_001302959.2 linkuse as main transcriptc.-38_-15delGCACCGTGCTGGACGACAGCCGGG 5_prime_UTR_variant 2/6 NP_001289888.1 O00170A0A804HKL7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AIPENST00000279146.8 linkuse as main transcriptc.140_163delGCACCGTGCTGGACGACAGCCGGG p.Gly47_Arg54del disruptive_inframe_deletion 2/61 NM_003977.4 ENSP00000279146.3 O00170

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251330
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461730
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000111
Hom.:
0

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 24, 2023This 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 submitterclinical testingAmbry GeneticsJun 20, 2024The 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 providedliterature onlyGeneReviews-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs267606537; hg19: chr11-67254514; API