rs2282885

Variant names:

• chr7-17305990-A-G
• rs2282885
• NM_001621.5:c.66-3946A>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.66-3946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,024 control chromosomes in the GnomAD database, including 6,993 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 0.27 (6993 hom., cov: 31)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• Publications: 12 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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.66-3946A>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.66-3946A>G		intron_variant	Intron 1 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.36-3946A>G		intron_variant	Intron 1 of 11	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40817 AN: 151906 Hom.: 6996 Cov.: 31

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.268 AC: 40797 AN: 152024 Hom.: 6993 Cov.: 31 AF XY: 0.267 AC XY: 19804 AN XY: 74300

African (AFR) AF: 0.0649 AC: 2696 AN: 41514

American (AMR) AF: 0.232 AC: 3543 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3466

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5164

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4820

European-Finnish (FIN) AF: 0.405 AC: 4275 AN: 10544

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26187 AN: 67932

Other (OTH) AF: 0.295 AC: 623 AN: 2110

Alfa AF: 0.338 Hom.: 26002

Bravo AF: 0.250

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2282885; hg19: chr7-17345614;