chr7-17334147-G-T

Position:

• chr7-17334147-G-T

Variant summary

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

The NM_001621.5(AHR):​c.908+33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,548,630 control chromosomes in the GnomAD database, including 12,418 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 0.13 (1487 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10931 hom.)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHR	NM_001621.5	c.908+33G>T		intron_variant		ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.908+33G>T		intron_variant		1	NM_001621.5	ENSP00000242057	P2
AHR	ENST00000463496.1	c.908+33G>T		intron_variant, NMD_transcript_variant		1		ENSP00000436466
AHR	ENST00000642825.1	c.863+33G>T		intron_variant				ENSP00000495987	A2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19423 AN: 151738 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.126 AC: 31312 AN: 247876 Hom.: 2485 AF XY: 0.124 AC XY: 16665 AN XY: 134276

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.347

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.0956

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.114 AC: 158538 AN: 1396774 Hom.: 10931 Cov.: 25 AF XY: 0.114 AC XY: 79324 AN XY: 698212

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0999

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.128 AC: 19435 AN: 151856 Hom.: 1487 Cov.: 32 AF XY: 0.131 AC XY: 9703 AN XY: 74240

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.0973

Gnomad4 OTH AF: 0.114

Alfa AF: 0.107 Hom.: 181

Bravo AF: 0.131

Asia WGS AF: 0.211 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2074113; hg19: chr7-17373771; COSMIC: COSV54126659; COSMIC: COSV54126659;