7-17298523-C-T

Position:

• chr7-17298523-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642825.1(AHR):​c.20+1899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 316,128 control chromosomes in the GnomAD database, including 7,455 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 0.23 (4389 hom., cov: 21)
  • Exomes 𝑓: 0.16 (3066 hom.)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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]

ENSG00000237773 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927609	XR_007060234.1	n.261+537G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.20+1899C>T		intron_variant				ENSP00000495987.1
ENSG00000237773	ENST00000433005.1	n.298+537G>A		intron_variant		2
ENSG00000237773	ENST00000643090.1	n.229+537G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.230 AC: 30732 AN: 133798 Hom.: 4366 Cov.: 21

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.162 AC: 29575 AN: 182264 Hom.: 3066 Cov.: 0 AF XY: 0.160 AC XY: 14859 AN XY: 92628

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.203

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.230 AC: 30805 AN: 133864 Hom.: 4389 Cov.: 21 AF XY: 0.235 AC XY: 14993 AN XY: 63902

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.203

Alfa AF: 0.0934 Hom.: 191

Bravo AF: 0.241

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.6
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10249788; hg19: chr7-17338147;