Genetic Variant AIP:c.468+111C>T (chr11-67489566-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_003977.4(AIP):c.468+111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,291,254 control chromosomes in the GnomAD database, including 91,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8511 hom., cov: 33)

Exomes 𝑓: 0.37 ( 82937 hom. )

Consequence

AIP
NM_003977.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.70

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 11-67489566-C-T is Benign according to our data. Variant chr11-67489566-C-T is described in ClinVar as [Benign]. Clinvar id is 1257908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AIP	NM_003977.4 link	c.468+111C>T	intron_variant	Intron 3 of 5	ENST00000279146.8	NP_003968.3	O00170
AIP	NM_001302960.2 link	c.468+111C>T	intron_variant	Intron 3 of 5		NP_001289889.1	O00170A0A804HJ38
AIP	NM_001302959.2 link	c.291+111C>T	intron_variant	Intron 3 of 5		NP_001289888.1	O00170A0A804HKL7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIP	ENST00000279146.8 link	c.468+111C>T		intron_variant	Intron 3 of 5	1	NM_003977.4	ENSP00000279146.3		O00170

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48766

AN:

152012

Hom.:

8512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.358

AC:

60144

AN:

168118

Hom.:

11446

AF XY:

0.351

AC XY:

32817

AN XY:

93424

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.513

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.368

GnomAD4 exome

AF:

0.373

AC:

425185

AN:

1139124

Hom.:

82937

Cov.:

AF XY:

0.368

AC XY:

211883

AN XY:

576380

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.350

GnomAD4 genome

AF:

0.321

AC:

48768

AN:

152130

Hom.:

8511

Cov.:

AF XY:

0.313

AC XY:

23278

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.313

Alfa

AF:

0.342

Hom.:

4768

Bravo

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.064

DANN

Benign

0.67

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