rs7796976

Variant names:

• chr7-17298806-A-G
• rs7796976
• NM_001621.5:c.-459A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-17298806-A-G
• chr7-17298806-A-T

Variant summary

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

The NM_001621.5(AHR):​c.-459A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 397,804 control chromosomes in the GnomAD database, including 118,847 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 0.79 (47879 hom., cov: 30)
  • Exomes 𝑓: 0.76 (70968 hom.)
• Consequence: AHR NM_001621.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 11 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

ENSG00000237773 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.-459A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	ENST00000242057.9	NP_001612.1
AHR	NM_001621.5	c.-459A>G		5_prime_UTR_variant	Exon 1 of 11	ENST00000242057.9	NP_001612.1
LOC101927609	XR_007060234.1	n.261+254T>C		intron_variant	Intron 1 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.-459A>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	1	NM_001621.5	ENSP00000242057.4
AHR	ENST00000242057.9	c.-459A>G		5_prime_UTR_variant	Exon 1 of 11	1	NM_001621.5	ENSP00000242057.4

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119925 AN: 151766 Hom.: 47842 Cov.: 30

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.785

GnomAD4 exome AF: 0.759 AC: 186654 AN: 245926 Hom.: 70968 Cov.: 0 AF XY: 0.758 AC XY: 94516 AN XY: 124722

African (AFR) AF: 0.900 AC: 6424 AN: 7136

American (AMR) AF: 0.718 AC: 5320 AN: 7412

Ashkenazi Jewish (ASJ) AF: 0.779 AC: 7167 AN: 9202

East Asian (EAS) AF: 0.682 AC: 15594 AN: 22874

South Asian (SAS) AF: 0.711 AC: 2190 AN: 3080

European-Finnish (FIN) AF: 0.778 AC: 16213 AN: 20832

Middle Eastern (MID) AF: 0.789 AC: 1021 AN: 1294

European-Non Finnish (NFE) AF: 0.762 AC: 120194 AN: 157758

Other (OTH) AF: 0.767 AC: 12531 AN: 16338

GnomAD4 genome AF: 0.790 AC: 120014 AN: 151878 Hom.: 47879 Cov.: 30 AF XY: 0.789 AC XY: 58536 AN XY: 74216

African (AFR) AF: 0.900 AC: 37356 AN: 41496

American (AMR) AF: 0.698 AC: 10672 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2635 AN: 3466

East Asian (EAS) AF: 0.667 AC: 3394 AN: 5090

South Asian (SAS) AF: 0.724 AC: 3480 AN: 4808

European-Finnish (FIN) AF: 0.792 AC: 8370 AN: 10572

Middle Eastern (MID) AF: 0.750 AC: 219 AN: 292

European-Non Finnish (NFE) AF: 0.759 AC: 51514 AN: 67846

Other (OTH) AF: 0.782 AC: 1655 AN: 2116

Alfa AF: 0.777 Hom.: 5743

Bravo AF: 0.790

Asia WGS AF: 0.704 AC: 2447 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.75
PhyloP100		0.58
PromoterAI		-0.082	Neutral
Mutation Taster		=299/1	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: rs7796976; hg19: chr7-17338430;