rs139459091

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_003977.4(AIP):c.26G>A(p.Arg9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,614,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

AIP
NM_003977.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:7B:2

Conservation

PhyloP100: 1.41

Publications

10 publications found

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]

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

AIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057757854).

BP6

Variant 11-67483184-G-A is Benign according to our data. Variant chr11-67483184-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 485052.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000381 (58/152356) while in subpopulation AMR AF = 0.00222 (34/15300). AF 95% confidence interval is 0.00163. There are 0 homozygotes in GnomAd4. There are 26 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 58 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	NM_003977.4	MANE Select	c.26G>A	p.Arg9Gln	missense	Exon 1 of 6	NP_003968.3	O00170
	AIP	NM_001302960.2		c.26G>A	p.Arg9Gln	missense	Exon 1 of 6	NP_001289889.1	A0A804HJ38

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AIP	ENST00000279146.8	TSL:1 MANE Select	c.26G>A	p.Arg9Gln	missense	Exon 1 of 6	ENSP00000279146.3	O00170
AIP	ENST00000934218.1		c.26G>A	p.Arg9Gln	missense	Exon 1 of 6	ENSP00000604277.1
AIP	ENST00000872352.1		c.26G>A	p.Arg9Gln	missense	Exon 1 of 6	ENSP00000542411.1

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000263

AC:

AN:

251426

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000198

AC:

289

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

144

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.000738

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000191

AC:

212

AN:

1111994

Other (OTH)

AF:

0.000497

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000381

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41596

American (AMR)

AF:

0.00222

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000220

AC:

AN:

68036

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000322

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Hereditary cancer-predisposing syndrome (2)

Pituitary dependent hypercortisolism;C1863342:Acroleukopathy, symmetric;C4538355:Somatotroph adenoma (1)

Somatotroph adenoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.058

MetaSVM

Uncertain

-0.092

PhyloP100

1.4

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.50

REVEL

Benign

0.24

Sift

Uncertain

0.026

Sift4G

Benign

0.54

Vest4

0.28

MVP

0.74

MPC

0.45

ClinPred

0.072

GERP RS

4.8

PromoterAI

-0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.30

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over