11-67490085-C-T

Position:

chr11-67490085-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003977.4(AIP):c.516C>T(p.Asp172Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,611,554 control chromosomes in the GnomAD database, including 1,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 129 hom., cov: 33)

Exomes 𝑓: 0.021 ( 904 hom. )

Consequence

AIP
NM_003977.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.88

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 11-67490085-C-T is Benign according to our data. Variant chr11-67490085-C-T is described in ClinVar as [Benign]. Clinvar id is 305728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67490085-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 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.516C>T	p.Asp172Asp	synonymous_variant	4/6	ENST00000279146.8	NP_003968.3	O00170
AIP	NM_001302960.2 linkuse as main transcript	c.516C>T	p.Asp172Asp	synonymous_variant	4/6		NP_001289889.1	O00170A0A804HJ38
AIP	NM_001302959.2 linkuse as main transcript	c.339C>T	p.Asp113Asp	synonymous_variant	4/6		NP_001289888.1	O00170A0A804HKL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIP	ENST00000279146.8 linkuse as main transcript	c.516C>T	p.Asp172Asp	synonymous_variant	4/6	1	NM_003977.4	ENSP00000279146.3		O00170

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4941

AN:

152150

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.0366

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0141

Gnomad OTH

AF:

0.0288

GnomAD3 exomes

AF:

0.0338

AC:

8325

AN:

245994

Hom.:

264

AF XY:

0.0328

AC XY:

4386

AN XY:

133558

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.0250

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.0386

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0209

AC:

30542

AN:

1459286

Hom.:

904

Cov.:

AF XY:

0.0212

AC XY:

15386

AN XY:

725752

show subpopulations

Gnomad4 AFR exome

AF:

0.0477

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.0273

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.0360

Gnomad4 FIN exome

AF:

0.0608

Gnomad4 NFE exome

AF:

0.0116

Gnomad4 OTH exome

AF:

0.0267

GnomAD4 genome

AF:

0.0325

AC:

4955

AN:

152268

Hom.:

129

Cov.:

AF XY:

0.0352

AC XY:

2621

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0451

Gnomad4 AMR

AF:

0.0245

Gnomad4 ASJ

AF:

0.0317

Gnomad4 EAS

AF:

0.126

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0706

Gnomad4 NFE

AF:

0.0141

Gnomad4 OTH

AF:

0.0304

Alfa

AF:

0.0211

Hom.:

Bravo

AF:

0.0305

Asia WGS

AF:

0.0830

AC:

287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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. -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Aug 12, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 13, 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

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.1

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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