7-17196176-G-T

Variant names:

• chr7-17196176-G-T
• rs6950788
• ENST00000642825.1:c.-1018-8527G>T

Variant summary

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

The ENST00000642825.1(AHR):​c.-1018-8527G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 151,958 control chromosomes in the GnomAD database, including 41,852 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 0.73 (41852 hom., cov: 32)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000642825.1		c.-1018-8527G>T		intron	N/A	ENSP00000495987.1
	ENSG00000237773	ENST00000433005.2	TSL:2	n.650-27585C>A		intron	N/A
	ENSG00000237773	ENST00000643090.1		n.306+63076C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110626 AN: 151840 Hom.: 41839 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.904

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.801

Gnomad OTH AF: 0.784

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

GnomAD4 genome AF: 0.728 AC: 110673 AN: 151958 Hom.: 41852 Cov.: 32 AF XY: 0.730 AC XY: 54228 AN XY: 74252

African (AFR) AF: 0.515 AC: 21308 AN: 41400

American (AMR) AF: 0.858 AC: 13103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.974 AC: 5040 AN: 5172

South Asian (SAS) AF: 0.905 AC: 4359 AN: 4818

European-Finnish (FIN) AF: 0.664 AC: 7000 AN: 10548

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.801 AC: 54461 AN: 67956

Other (OTH) AF: 0.786 AC: 1661 AN: 2114

Alfa AF: 0.784 Hom.: 127094

Bravo AF: 0.734

Asia WGS AF: 0.896 AC: 3113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.75
DANN	Benign	0.33
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs6950788; hg19: chr7-17235800;