rs2040623

chr7-17341038-A-C

Variant summary

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

The NM_001621.5(AHR):c.2403+810A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,006 control chromosomes in the GnomAD database, including 3,889 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 0.22 (3889 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHR	NM_001621.5	c.2403+810A>C		intron_variant		ENST00000242057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHR	ENST00000242057.9	c.2403+810A>C		intron_variant		1	NM_001621.5	P2
AHR	ENST00000463496.1	c.2403+810A>C		intron_variant, NMD_transcript_variant		1
AHR	ENST00000642825.1	c.2358+810A>C		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32854 AN: 151890 Hom.: 3881 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.216 AC: 32876 AN: 152006 Hom.: 3889 Cov.: 32 AF XY: 0.218 AC XY: 16217 AN XY: 74326

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.222

Alfa AF: 0.216 Hom.: 5011

Bravo AF: 0.228

Asia WGS AF: 0.295 AC: 1024 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.86

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: rs2040623; hg19: chr7-17380662;