rs641081

Positions:

chr11-67490352-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003977.4(AIP):c.682C>A(p.Gln228Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,612,358 control chromosomes in the GnomAD database, including 771,770 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 59219 hom., cov: 31)

Exomes 𝑓: 0.98 ( 712551 hom. )

Consequence

AIP
NM_003977.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.30

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 links:

AIP (HGNC:):

AIP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.653613E-7).

BP6

Variant 11-67490352-C-A is Benign according to our data. Variant chr11-67490352-C-A is described in ClinVar as [Benign]. Clinvar id is 259205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67490352-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIP	NM_003977.4 linkuse as main transcript	c.682C>A	p.Gln228Lys	missense_variant	5/6	ENST00000279146.8	NP_003968.3	O00170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIP	ENST00000279146.8 linkuse as main transcript	c.682C>A	p.Gln228Lys	missense_variant	5/6	1	NM_003977.4	ENSP00000279146.3		O00170

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129700

AN:

151904

Hom.:

59183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.938

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.997

Gnomad OTH

AF:

0.893

GnomAD3 exomes

AF:

0.962

AC:

239149

AN:

248548

Hom.:

116991

AF XY:

0.972

AC XY:

131304

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.493

Gnomad AMR exome

AF:

0.973

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.999

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.998

Gnomad OTH exome

AF:

0.980

GnomAD4 exome

AF:

0.985

AC:

1438064

AN:

1460336

Hom.:

712551

Cov.:

AF XY:

0.987

AC XY:

716902

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.490

Gnomad4 AMR exome

AF:

0.970

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.998

Gnomad4 OTH exome

AF:

0.968

GnomAD4 genome

AF:

0.854

AC:

129792

AN:

152022

Hom.:

59219

Cov.:

AF XY:

0.860

AC XY:

63868

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.496

Gnomad4 AMR

AF:

0.938

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.997

Gnomad4 OTH

AF:

0.894

Alfa

AF:

0.968

Hom.:

103160

Bravo

AF:

0.836

TwinsUK

AF:

0.999

AC:

3705

ALSPAC

AF:

0.997

AC:

3843

ESP6500AA

AF:

0.517

AC:

2277

ESP6500EA

AF:

0.997

AC:

8560

ExAC

AF:

0.954

AC:

115509

Asia WGS

AF:

0.977

AC:

3399

AN:

3478

EpiCase

AF:

0.998

EpiControl

AF:

0.997

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 11, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Somatotroph adenoma

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.0060

T;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

T;T;T

MetaRNN

Benign

9.7e-7

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.46

PROVEAN

Benign

0.69

N;N;.

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.089

MPC

0.46

ClinPred

0.0016

GERP RS

1.1

gMVP

0.31

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over