chr7-17024683-C-G

Variant names:

• chr7-17024683-C-G
• rs7804595
• ENST00000643090.1:n.307-52937G>C

Variant summary

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

The ENST00000643090.1(ENSG00000237773):​n.307-52937G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,964 control chromosomes in the GnomAD database, including 6,115 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 0.26 (6115 hom., cov: 32)
• Consequence: ENSG00000237773 ENST00000643090.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901595	XR_007060239.1	n.13339+11005G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000643090.1	n.307-52937G>C		intron_variant	Intron 2 of 2
AHR	ENST00000645559.1	n.30+108295C>G		intron_variant	Intron 1 of 1
ENSG00000289189	ENST00000766378.1	n.277+34283C>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38757 AN: 151846 Hom.: 6112 Cov.: 32

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.255 AC: 38761 AN: 151964 Hom.: 6115 Cov.: 32 AF XY: 0.259 AC XY: 19223 AN XY: 74274

African (AFR) AF: 0.0875 AC: 3631 AN: 41488

American (AMR) AF: 0.399 AC: 6078 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 824 AN: 3466

East Asian (EAS) AF: 0.129 AC: 665 AN: 5170

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4818

European-Finnish (FIN) AF: 0.339 AC: 3582 AN: 10558

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21668 AN: 67910

Other (OTH) AF: 0.254 AC: 536 AN: 2114

Alfa AF: 0.149 Hom.: 296

Bravo AF: 0.254

Asia WGS AF: 0.214 AC: 744 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.51
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs7804595; hg19: chr7-17064307;