rs11822907

Variant names:

• chr11-67487038-C-T
• rs11822907
• NM_003977.4:c.132C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-67487038-C-T
• chr11-67487038-C-A

Variant summary

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

The NM_001302959.2(AIP):​c.-46C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,613,994 control chromosomes in the GnomAD database, including 249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (140 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (109 hom.)
• Consequence: AIP NM_001302959.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -2.47
• Publications: 4 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=-0.71).
• BP6: Variant 11-67487038-C-T is Benign according to our data. Variant chr11-67487038-C-T is described in ClinVar as Benign. ClinVar VariationId is 259204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302959.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	NM_003977.4	MANE Select	c.132C>T	p.Asp44Asp	synonymous	Exon 2 of 6	NP_003968.3	O00170
	AIP	NM_001302959.2		c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001289888.1	A0A804HKL7
	AIP	NM_001302960.2		c.132C>T	p.Asp44Asp	synonymous	Exon 2 of 6	NP_001289889.1	A0A804HJ38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	ENST00000279146.8	TSL:1 MANE Select	c.132C>T	p.Asp44Asp	synonymous	Exon 2 of 6	ENSP00000279146.3	O00170
	AIP	ENST00000683856.1		c.-46C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000507979.1	A0A804HKL7
	AIP	ENST00000934218.1		c.132C>T	p.Asp44Asp	synonymous	Exon 2 of 6	ENSP00000604277.1

Frequencies

GnomAD3 genomes AF: 0.0215 AC: 3278 AN: 152166 Hom.: 140 Cov.: 33

Gnomad AFR AF: 0.0749

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00604 AC: 1518 AN: 251316 AF XY: 0.00439

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00235 AC: 3428 AN: 1461710 Hom.: 109 Cov.: 32 AF XY: 0.00202 AC XY: 1472 AN XY: 727142

African (AFR) AF: 0.0802 AC: 2686 AN: 33480

American (AMR) AF: 0.00452 AC: 202 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

Middle Eastern (MID) AF: 0.00329 AC: 19 AN: 5768

European-Non Finnish (NFE) AF: 0.000203 AC: 226 AN: 1112006

Other (OTH) AF: 0.00457 AC: 276 AN: 60394

GnomAD4 genome AF: 0.0216 AC: 3283 AN: 152284 Hom.: 140 Cov.: 33 AF XY: 0.0215 AC XY: 1600 AN XY: 74464

African (AFR) AF: 0.0748 AC: 3104 AN: 41524

American (AMR) AF: 0.00784 AC: 120 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68042

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0111 Hom.: 55

Bravo AF: 0.0243

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Somatotroph adenoma (2)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.0
DANN	Benign	0.89
PhyloP100		-2.5
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: rs11822907; hg19: chr11-67254509;