rs4410790

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060234.1	n.922+14299A>G		intron_variant	Intron 6 of 11
LOC101927609	XR_007060235.1	n.786+14299A>G		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-955-2021T>C		intron_variant	Intron 2 of 14			ENSP00000495987.1
ENSG00000237773	ENST00000433005.2	n.649+14299A>G		intron_variant	Intron 3 of 5	2
ENSG00000237773	ENST00000643090.1	n.306+14299A>G		intron_variant	Intron 2 of 2

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 v4.3

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;