rs2276020

Positions:

• chr11-67490085-C-G
• chr11-67490085-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003977.4(AIP):​c.516C>G​(p.Asp172Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,328 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D172D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AIP NM_003977.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIP	NM_003977.4	c.516C>G	p.Asp172Glu	missense_variant	4/6	ENST00000279146.8
AIP	NM_001302960.2	c.516C>G	p.Asp172Glu	missense_variant	4/6
AIP	NM_001302959.2	c.339C>G	p.Asp113Glu	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIP	ENST00000279146.8	c.516C>G	p.Asp172Glu	missense_variant	4/6	1	NM_003977.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459328 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725776

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	0.37
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.86	D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	0.000011	P
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N;N;.
REVEL	Uncertain	0.47
Sift	Benign	0.75	T;T;.
Sift4G	Benign	0.48	T;T;T
Vest4		0.50
MutPred		0.36		.;Loss of helix (P = 0.079);.;
MVP		0.73
MPC		1.1
ClinPred		0.91	D
GERP RS		-4.4
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2276020; hg19: chr11-67257556;