rs4719497

Positions:

• chr7-17295275-T-C

Variant summary

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

The ENST00000642825.1(AHR):​c.-202-1022T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,234 control chromosomes in the GnomAD database, including 997 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 0.097 (997 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927609	XR_007060230.1	n.113-2A>G		splice_acceptor_variant, intron_variant
LOC101927609	XR_007060231.1	n.113-2A>G		splice_acceptor_variant, intron_variant
LOC101927609	XR_007060232.1	n.113-2A>G		splice_acceptor_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-202-1022T>C		intron_variant				ENSP00000495987.1
ENSG00000237773	ENST00000654641.1	n.2034A>G		non_coding_transcript_exon_variant	1/3
ENSG00000237773	ENST00000665788.1	n.2051A>G		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14696 AN: 152116 Hom.: 999 Cov.: 31

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0966

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0965 AC: 14695 AN: 152234 Hom.: 997 Cov.: 31 AF XY: 0.0948 AC XY: 7060 AN XY: 74438

Gnomad4 AFR AF: 0.0248

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0610

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.0960

Alfa AF: 0.128 Hom.: 1764

Bravo AF: 0.0964

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4719497; hg19: chr7-17334899;