rs1523632

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901595	XR_007060239.1	n.13339+5344C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000643090.1	n.307-58598C>T		intron_variant	Intron 2 of 2
AHR	ENST00000645559.1	n.30+113956G>A		intron_variant	Intron 1 of 1
ENSG00000289189	ENST00000766378.1	n.277+39944G>A		intron_variant	Intron 1 of 1

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 v4.3

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;