7-17331739-A-G

Variant names:

• chr7-17331739-A-G
• rs7811989
• NM_001621.5:c.705+853A>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.705+853A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 151,848 control chromosomes in the GnomAD database, including 44,741 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 0.76 (44741 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.705+853A>G		intron_variant	Intron 6 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.705+853A>G		intron_variant	Intron 6 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.675+853A>G		intron_variant	Intron 6 of 11	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115575 AN: 151730 Hom.: 44695 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.762 AC: 115667 AN: 151848 Hom.: 44741 Cov.: 32 AF XY: 0.760 AC XY: 56437 AN XY: 74232

African (AFR) AF: 0.872 AC: 36181 AN: 41506

American (AMR) AF: 0.568 AC: 8632 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2610 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3961 AN: 5182

South Asian (SAS) AF: 0.696 AC: 3350 AN: 4810

European-Finnish (FIN) AF: 0.804 AC: 8512 AN: 10582

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.736 AC: 49904 AN: 67800

Other (OTH) AF: 0.751 AC: 1581 AN: 2104

Alfa AF: 0.732 Hom.: 57823

Bravo AF: 0.750

Asia WGS AF: 0.711 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.99
DANN	Benign	0.53
PhyloP100		-0.25
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: rs7811989; hg19: chr7-17371363;