Genetic Variant ENST00000682699.1:c.-220G>T (chr11-67482939-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000682699.1(AIP):c.-220G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000252 in 396,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000025 ( 0 hom. )

Consequence

AIP
ENST00000682699.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.58

Publications

0 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:

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ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682699.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	NM_003977.4	MANE Select	c.-220G>T		upstream_gene	N/A	NP_003968.3
	AIP	NM_001302960.2		c.-220G>T		upstream_gene	N/A	NP_001289889.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AIP	ENST00000682699.1		c.-220G>T	5_prime_UTR	Exon 3 of 8	ENSP00000507935.1
AIP	ENST00000279146.8	TSL:1 MANE Select	c.-220G>T	upstream_gene	N/A	ENSP00000279146.3
AIP	ENST00000525341.2	TSL:2	c.-244G>T	upstream_gene	N/A	ENSP00000476993.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000252

AC:

AN:

396478

Hom.:

AF XY:

0.00000477

AC XY:

AN XY:

209450

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

11562

American (AMR)

AF:

0.00

AC:

AN:

19228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12544

East Asian (EAS)

AF:

0.00

AC:

AN:

26402

South Asian (SAS)

AF:

0.00

AC:

AN:

47204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1726

European-Non Finnish (NFE)

AF:

0.00000430

AC:

AN:

232534

Other (OTH)

AF:

0.00

AC:

AN:

22860

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.47

(source)

DANN

Benign

0.72

PhyloP100

-3.6

PromoterAI

-0.017

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over