11-67489566-C-T

Variant names:

• chr11-67489566-C-T
• rs4084113
• NM_003977.4:c.468+111C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.70
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIP	NM_003977.4	c.468+111C>T		intron_variant	Intron 3 of 5	ENST00000279146.8	NP_003968.3
AIP	NM_001302960.2	c.468+111C>T		intron_variant	Intron 3 of 5		NP_001289889.1
AIP	NM_001302959.2	c.291+111C>T		intron_variant	Intron 3 of 5		NP_001289888.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48766 AN: 152012 Hom.: 8512 Cov.: 33

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

GnomAD2 exomes AF: 0.358 AC: 60144 AN: 168118 AF XY: 0.351

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 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.: 16 AF XY: 0.368 AC XY: 211883 AN XY: 576380

African (AFR) AF: 0.210 AC: 5683 AN: 27006

American (AMR) AF: 0.496 AC: 18805 AN: 37886

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6131 AN: 23754

East Asian (EAS) AF: 0.154 AC: 5495 AN: 35638

South Asian (SAS) AF: 0.246 AC: 18911 AN: 76950

European-Finnish (FIN) AF: 0.313 AC: 12589 AN: 40188

Middle Eastern (MID) AF: 0.339 AC: 1759 AN: 5196

European-Non Finnish (NFE) AF: 0.402 AC: 338371 AN: 842654

Other (OTH) AF: 0.350 AC: 17441 AN: 49852

GnomAD4 genome AF: 0.321 AC: 48768 AN: 152130 Hom.: 8511 Cov.: 33 AF XY: 0.313 AC XY: 23278 AN XY: 74370

African (AFR) AF: 0.209 AC: 8678 AN: 41518

American (AMR) AF: 0.399 AC: 6100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 924 AN: 3464

East Asian (EAS) AF: 0.169 AC: 872 AN: 5164

South Asian (SAS) AF: 0.231 AC: 1115 AN: 4824

European-Finnish (FIN) AF: 0.302 AC: 3200 AN: 10608

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26814 AN: 67942

Other (OTH) AF: 0.313 AC: 662 AN: 2112

Alfa AF: 0.346 Hom.: 5360

Bravo AF: 0.330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4084113; hg19: chr11-67257037; COSMIC: COSV54159710; COSMIC: COSV54159710;