rs2040623

Variant names:

• chr7-17341038-A-C
• rs2040623
• NM_001621.5:c.2403+810A>C

Variant summary

Our verdict is Benign. The variant received -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]

ENSG00000283321 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.2403+810A>C		intron_variant	Intron 10 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.2403+810A>C		intron_variant	Intron 10 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.2373+810A>C		intron_variant	Intron 10 of 11	5		ENSP00000490530.1
AHR	ENST00000463496.1	n.2403+810A>C		intron_variant	Intron 10 of 11	1		ENSP00000436466.1
AHR	ENST00000642825.1	c.2358+810A>C		intron_variant	Intron 14 of 14			ENSP00000495987.1

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 AC: 0.179675 AN: 0.179675

Gnomad4 AMR AF: 0.303 AC: 0.302699 AN: 0.302699

Gnomad4 ASJ AF: 0.173 AC: 0.173021 AN: 0.173021

Gnomad4 EAS AF: 0.414 AC: 0.414153 AN: 0.414153

Gnomad4 SAS AF: 0.286 AC: 0.286396 AN: 0.286396

Gnomad4 FIN AF: 0.169 AC: 0.168656 AN: 0.168656

Gnomad4 NFE AF: 0.210 AC: 0.209648 AN: 0.209648

Gnomad4 OTH AF: 0.222 AC: 0.222327 AN: 0.222327

Alfa AF: 0.217 Hom.: 6365

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
Mutation Taster		=100/0	polymorphism (auto)

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;