NM_001621.5:c.450+613G>A

Variant names:

• chr7-17328461-G-A
• rs6960165
• NM_001621.5:c.450+613G>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.450+613G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 151,848 control chromosomes in the GnomAD database, including 50,648 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 0.81 (50648 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 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.450+613G>A		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.450+613G>A		intron	N/A	ENSP00000242057.4
	ENSG00000283321	ENST00000637807.1	TSL:5	c.420+613G>A		intron	N/A	ENSP00000490530.1
	AHR	ENST00000463496.1	TSL:1	n.450+613G>A		intron	N/A	ENSP00000436466.1

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123147 AN: 151730 Hom.: 50589 Cov.: 32

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.812 AC: 123263 AN: 151848 Hom.: 50648 Cov.: 32 AF XY: 0.813 AC XY: 60327 AN XY: 74238

African (AFR) AF: 0.944 AC: 39185 AN: 41510

American (AMR) AF: 0.709 AC: 10774 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2606 AN: 3464

East Asian (EAS) AF: 0.795 AC: 4106 AN: 5168

South Asian (SAS) AF: 0.844 AC: 4072 AN: 4826

European-Finnish (FIN) AF: 0.806 AC: 8543 AN: 10598

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51382 AN: 67772

Other (OTH) AF: 0.796 AC: 1674 AN: 2102

Alfa AF: 0.775 Hom.: 165752

Bravo AF: 0.810

Asia WGS AF: 0.803 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.16
DANN	Benign	0.39
PhyloP100		-0.88
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: rs6960165; hg19: chr7-17368085;