rs7806681

Variant names:

• chr7-17188498-C-T
• rs7806681
• ENST00000642825.1:c.-1018-16205C>T

Variant summary

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

The ENST00000642825.1(AHR):​c.-1018-16205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,802 control chromosomes in the GnomAD database, including 21,282 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 0.53 (21282 hom., cov: 32)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107986772	XR_001745107.2	n.60-16205C>T		intron_variant	Intron 1 of 2
LOC101927609	XR_007060234.1	n.923-19907G>A		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-1018-16205C>T		intron_variant	Intron 1 of 14			ENSP00000495987.1
ENSG00000237773	ENST00000433005.2	n.650-19907G>A		intron_variant	Intron 3 of 5	2
ENSG00000237773	ENST00000643090.1	n.306+70754G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80050 AN: 151684 Hom.: 21281 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.528 AC: 80094 AN: 151802 Hom.: 21282 Cov.: 32 AF XY: 0.526 AC XY: 39014 AN XY: 74186

African (AFR) AF: 0.461 AC: 19068 AN: 41406

American (AMR) AF: 0.524 AC: 7990 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1961 AN: 3466

East Asian (EAS) AF: 0.656 AC: 3394 AN: 5172

South Asian (SAS) AF: 0.547 AC: 2632 AN: 4812

European-Finnish (FIN) AF: 0.474 AC: 4999 AN: 10546

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38207 AN: 67852

Other (OTH) AF: 0.560 AC: 1178 AN: 2104

Alfa AF: 0.541 Hom.: 28259

Bravo AF: 0.530

Asia WGS AF: 0.595 AC: 2069 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.7
DANN	Benign	0.66
PhyloP100		0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7806681; hg19: chr7-17228122;