7-17293365-C-T

Variant names:

• chr7-17293365-C-T
• rs10250822
• ENST00000642825.1:c.-202-2932C>T

Variant summary

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

The ENST00000642825.1(AHR):​c.-202-2932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 151,948 control chromosomes in the GnomAD database, including 47,564 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 (47564 hom., cov: 30)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060230.1	n.220+1801G>A		intron_variant	Intron 2 of 5
LOC101927609	XR_007060231.1	n.220+1801G>A		intron_variant	Intron 2 of 4
LOC101927609	XR_007060232.1	n.220+1801G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-202-2932C>T		intron_variant	Intron 3 of 14			ENSP00000495987.1
ENSG00000237773	ENST00000415246.3	n.267+1801G>A		intron_variant	Intron 2 of 3	3
ENSG00000237773	ENST00000419382.7	n.154+4987G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119581 AN: 151830 Hom.: 47530 Cov.: 30

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.788 AC: 119669 AN: 151948 Hom.: 47564 Cov.: 30 AF XY: 0.785 AC XY: 58308 AN XY: 74258

African (AFR) AF: 0.893 AC: 37025 AN: 41464

American (AMR) AF: 0.698 AC: 10646 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2610 AN: 3470

East Asian (EAS) AF: 0.632 AC: 3262 AN: 5162

South Asian (SAS) AF: 0.715 AC: 3449 AN: 4822

European-Finnish (FIN) AF: 0.797 AC: 8409 AN: 10546

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51684 AN: 67914

Other (OTH) AF: 0.780 AC: 1644 AN: 2108

Alfa AF: 0.765 Hom.: 50588

Bravo AF: 0.786

Asia WGS AF: 0.682 AC: 2371 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		0.016

Splicing

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

Other links and lift over

dbSNP: rs10250822; hg19: chr7-17332989;