rs188965257

Variant names:

• chr11-67490967-C-A
• rs188965257
• NM_003977.4:c.967C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67490967-C-A
• chr11-67490967-C-G
• chr11-67490967-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_003977.4(AIP):​c.967C>A​(p.Arg323Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R323R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AIP NM_003977.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-67490967-C-A is Benign according to our data. Variant chr11-67490967-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3279528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.72 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003977.4. 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.967C>A	p.Arg323Arg	synonymous	Exon 6 of 6	NP_003968.3
	AIP	NM_001302959.2		c.790C>A	p.Arg264Arg	synonymous	Exon 6 of 6	NP_001289888.1
	AIP	NM_001302960.2		c.*107C>A		3_prime_UTR	Exon 6 of 6	NP_001289889.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIP	ENST00000279146.8	TSL:1 MANE Select	c.967C>A	p.Arg323Arg	synonymous	Exon 6 of 6	ENSP00000279146.3
	AIP	ENST00000683856.1		c.790C>A	p.Arg264Arg	synonymous	Exon 6 of 6	ENSP00000507979.1
	AIP	ENST00000684657.1		c.787C>A	p.Arg263Arg	synonymous	Exon 5 of 5	ENSP00000507961.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456540 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724256

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 85666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51676

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110176

Other (OTH) AF: 0.00 AC: 0 AN: 60174

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs188965257; hg19: chr11-67258438;