rs2237297

Variant names:

• chr7-17319970-G-A
• rs2237297
• NM_001621.5:c.254-2531G>A

Variant summary

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

The NM_001621.5(AHR):​c.254-2531G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,918 control chromosomes in the GnomAD database, including 1,483 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 0.13 (1483 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.254-2531G>A		intron_variant	Intron 2 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.254-2531G>A		intron_variant	Intron 2 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.224-2531G>A		intron_variant	Intron 2 of 11	5		ENSP00000490530.1
AHR	ENST00000463496.1	n.254-2531G>A		intron_variant	Intron 2 of 11	1		ENSP00000436466.1
AHR	ENST00000642825.1	c.209-2531G>A		intron_variant	Intron 6 of 14			ENSP00000495987.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19432 AN: 151798 Hom.: 1481 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0980

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.128 AC: 19440 AN: 151918 Hom.: 1483 Cov.: 32 AF XY: 0.131 AC XY: 9729 AN XY: 74254

African (AFR) AF: 0.151 AC: 6272 AN: 41416

American (AMR) AF: 0.120 AC: 1836 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1928 AN: 5162

South Asian (SAS) AF: 0.158 AC: 763 AN: 4822

European-Finnish (FIN) AF: 0.115 AC: 1219 AN: 10558

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0980 AC: 6654 AN: 67932

Other (OTH) AF: 0.114 AC: 240 AN: 2114

Alfa AF: 0.102 Hom.: 854

Bravo AF: 0.130

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.71
DANN	Benign	0.77
PhyloP100		-0.23
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: rs2237297; hg19: chr7-17359594;