chr7-17030344-G-A

Variant names:

• chr7-17030344-G-A
• rs1523632
• ENST00000643090.1:n.307-58598C>T

Variant summary

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

The ENST00000643090.1(ENSG00000237773):​n.307-58598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,058 control chromosomes in the GnomAD database, including 19,585 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 0.48 (19585 hom., cov: 33)
• Consequence: ENSG00000237773 ENST00000643090.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 4 publications found

Genes affected

ENSG00000237773 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643090.1. 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
	ENSG00000237773	ENST00000643090.1		n.307-58598C>T		intron	N/A
	AHR	ENST00000645559.1		n.30+113956G>A		intron	N/A
	ENSG00000289189	ENST00000766378.1		n.277+39944G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73687 AN: 151940 Hom.: 19578 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.610

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.485 AC: 73697 AN: 152058 Hom.: 19585 Cov.: 33 AF XY: 0.492 AC XY: 36559 AN XY: 74340

African (AFR) AF: 0.256 AC: 10612 AN: 41492

American (AMR) AF: 0.655 AC: 10009 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1561 AN: 3466

East Asian (EAS) AF: 0.521 AC: 2693 AN: 5168

South Asian (SAS) AF: 0.498 AC: 2402 AN: 4822

European-Finnish (FIN) AF: 0.610 AC: 6445 AN: 10574

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38336 AN: 67938

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.540 Hom.: 97015

Bravo AF: 0.480

Asia WGS AF: 0.505 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.57
PhyloP100		-0.50

Splicing

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

Other links and lift over

dbSNP: rs1523632; hg19: chr7-17069968;