rs2282886

Variant names:

• chr7-17303781-A-G
• rs2282886
• NM_001621.5:c.65+4452A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001621.5(AHR):​c.65+4452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,854 control chromosomes in the GnomAD database, including 21,261 homozygotes. 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: 𝑓 0.50 (21261 hom., cov: 31)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 2 publications found

Genes affected

AHR (HGNC:348): (aryl hydrocarbon receptor) The protein encoded by this gene is a ligand-activated helix-loop-helix transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. Before ligand binding, the encoded protein is sequestered in the cytoplasm; upon ligand binding, this protein moves to the nucleus and stimulates transcription of target genes. [provided by RefSeq, Sep 2015]

AHR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 85

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• foveal hypoplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000283321 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.65+4452A>G		intron_variant	Intron 1 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.65+4452A>G		intron_variant	Intron 1 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.35+4452A>G		intron_variant	Intron 1 of 11	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76106 AN: 151736 Hom.: 21265 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.543

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.501 AC: 76088 AN: 151854 Hom.: 21261 Cov.: 31 AF XY: 0.502 AC XY: 37235 AN XY: 74240

African (AFR) AF: 0.272 AC: 11289 AN: 41456

American (AMR) AF: 0.386 AC: 5893 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2187 AN: 3466

East Asian (EAS) AF: 0.411 AC: 2128 AN: 5172

South Asian (SAS) AF: 0.542 AC: 2612 AN: 4820

European-Finnish (FIN) AF: 0.684 AC: 7214 AN: 10554

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42867 AN: 67820

Other (OTH) AF: 0.542 AC: 1143 AN: 2108

Alfa AF: 0.558 Hom.: 3381

Bravo AF: 0.469

Asia WGS AF: 0.468 AC: 1626 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.35
PhyloP100		0.043
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: rs2282886; hg19: chr7-17343405;