rs2282886

chr7-17303781-A-G

Variant summary

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

The NM_001621.5(AHR):c.65+4452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,854 control chromosomes in the GnomAD database, including 21,261 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 0.50 (21261 hom., cov: 31)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHR	NM_001621.5	c.65+4452A>G		intron_variant		ENST00000242057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHR	ENST00000242057.9	c.65+4452A>G		intron_variant		1	NM_001621.5	P2
AHR	ENST00000463496.1	c.65+4452A>G		intron_variant, NMD_transcript_variant		1
AHR	ENST00000642825.1	c.21-6155A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76106 AN: 151736 Hom.: 21265 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.501 AC: 76088 AN: 151854 Hom.: 21261 Cov.: 31 AF XY: 0.502 AC XY: 37235 AN XY: 74240

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.542

Alfa AF: 0.569 Hom.: 3353

Bravo AF: 0.469

Asia WGS AF: 0.468 AC: 1626 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.2
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2282886; hg19: chr7-17343405;