7-17244953-T-C

Variant names:

• chr7-17244953-T-C
• rs4410790
• ENST00000642825.1:c.-955-2021T>C

Variant summary

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

The ENST00000642825.1(AHR):​c.-955-2021T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,920 control chromosomes in the GnomAD database, including 23,243 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 0.54 (23243 hom., cov: 31)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 118 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642825.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000642825.1		c.-955-2021T>C		intron	N/A	ENSP00000495987.1
	ENSG00000237773	ENST00000433005.2	TSL:2	n.649+14299A>G		intron	N/A
	ENSG00000237773	ENST00000643090.1		n.306+14299A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82207 AN: 151802 Hom.: 23226 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.541 AC: 82252 AN: 151920 Hom.: 23243 Cov.: 31 AF XY: 0.539 AC XY: 40003 AN XY: 74264

African (AFR) AF: 0.455 AC: 18847 AN: 41402

American (AMR) AF: 0.387 AC: 5910 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1518 AN: 3472

East Asian (EAS) AF: 0.421 AC: 2178 AN: 5172

South Asian (SAS) AF: 0.438 AC: 2105 AN: 4810

European-Finnish (FIN) AF: 0.692 AC: 7304 AN: 10554

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42536 AN: 67940

Other (OTH) AF: 0.548 AC: 1154 AN: 2104

Alfa AF: 0.593 Hom.: 90760

Bravo AF: 0.517

Asia WGS AF: 0.450 AC: 1557 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.77
PhyloP100		0.26

Splicing

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

Other links and lift over

dbSNP: rs4410790; hg19: chr7-17284577;