NM_001621.5:c.66-1441T>C

Variant names:

• chr7-17308495-T-C
• rs2237298
• NM_001621.5:c.66-1441T>C

Variant summary

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

The NM_001621.5(AHR):​c.66-1441T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,030 control chromosomes in the GnomAD database, including 25,255 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 0.57 (25255 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001621.5. 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
	AHR	NM_001621.5	MANE Select	c.66-1441T>C		intron	N/A	NP_001612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000242057.9	TSL:1 MANE Select	c.66-1441T>C		intron	N/A	ENSP00000242057.4
	ENSG00000283321	ENST00000637807.1	TSL:5	c.36-1441T>C		intron	N/A	ENSP00000490530.1
	AHR	ENST00000463496.1	TSL:1	n.66-1441T>C		intron	N/A	ENSP00000436466.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86406 AN: 151912 Hom.: 25252 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.569 AC: 86434 AN: 152030 Hom.: 25255 Cov.: 32 AF XY: 0.566 AC XY: 42083 AN XY: 74314

African (AFR) AF: 0.516 AC: 21399 AN: 41474

American (AMR) AF: 0.415 AC: 6331 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2183 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2007 AN: 5176

South Asian (SAS) AF: 0.546 AC: 2629 AN: 4818

European-Finnish (FIN) AF: 0.677 AC: 7153 AN: 10568

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.628 AC: 42705 AN: 67954

Other (OTH) AF: 0.589 AC: 1239 AN: 2104

Alfa AF: 0.599 Hom.: 34535

Bravo AF: 0.547

Asia WGS AF: 0.474 AC: 1650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.82
PhyloP100		0.47
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: rs2237298; hg19: chr7-17348119;