rs2282885

chr7-17305990-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.66-3946A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,024 control chromosomes in the GnomAD database, including 6,993 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 0.27 (6993 hom., cov: 31)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHR	NM_001621.5	c.66-3946A>G		intron_variant		ENST00000242057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHR	ENST00000242057.9	c.66-3946A>G		intron_variant		1	NM_001621.5	P2
AHR	ENST00000463496.1	c.66-3946A>G		intron_variant, NMD_transcript_variant		1
AHR	ENST00000642825.1	c.21-3946A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40817 AN: 151906 Hom.: 6996 Cov.: 31

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.268 AC: 40797 AN: 152024 Hom.: 6993 Cov.: 31 AF XY: 0.267 AC XY: 19804 AN XY: 74300

Gnomad4 AFR AF: 0.0649

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.295

Alfa AF: 0.353 Hom.: 20218

Bravo AF: 0.250

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2282885; hg19: chr7-17345614;