rs181969066

Variant names:

• chr11-67487041-C-A
• rs181969066
• NM_003977.4:c.135C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67487041-C-A
• chr11-67487041-C-G
• chr11-67487041-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003977.4(AIP):​c.135C>A​(p.Asp45Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D45N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AIP NM_003977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 0 publications found

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]

AIP Gene-Disease associations (from GenCC):

• growth hormone secreting pituitary adenoma 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• familial isolated pituitary adenoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• pituitary gigantism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acromegaly

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034719467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIP	NM_003977.4	c.135C>A	p.Asp45Glu	missense_variant	Exon 2 of 6	ENST00000279146.8	NP_003968.3
AIP	NM_001302960.2	c.135C>A	p.Asp45Glu	missense_variant	Exon 2 of 6		NP_001289889.1
AIP	NM_001302959.2	c.-43C>A		5_prime_UTR_variant	Exon 2 of 6		NP_001289888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIP	ENST00000279146.8	c.135C>A	p.Asp45Glu	missense_variant	Exon 2 of 6	1	NM_003977.4	ENSP00000279146.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251312 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.11
DANN	Benign	0.82
DEOGEN2	Benign	0.0071	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.020	T;T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-0.65	T
PhyloP100		-0.37
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.22	N;N
REVEL	Benign	0.19
Sift	Benign	0.70	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.092
MutPred		0.36		Gain of solvent accessibility (P = 0.0155);Gain of solvent accessibility (P = 0.0155);
MVP		0.41
MPC		0.33
ClinPred		0.050	T
GERP RS		-2.4
gMVP		0.19
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs181969066; hg19: chr11-67254512;