7-17334147-G-T

Variant names:

• chr7-17334147-G-T
• rs2074113
• NM_001621.5:c.908+33G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

AHR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 85

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• foveal hypoplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000283321 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	NM_001621.5	MANE Select	c.908+33G>T		intron	N/A	NP_001612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000242057.9	TSL:1 MANE Select	c.908+33G>T		intron	N/A	ENSP00000242057.4
	ENSG00000283321	ENST00000637807.1	TSL:5	c.878+33G>T		intron	N/A	ENSP00000490530.1
	AHR	ENST00000463496.1	TSL:1	n.908+33G>T		intron	N/A	ENSP00000436466.1

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

GnomAD2 exomes AF: 0.126 AC: 31312 AN: 247876 AF XY: 0.124

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 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

African (AFR) AF: 0.159 AC: 5095 AN: 31988

American (AMR) AF: 0.110 AC: 4892 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2912 AN: 25686

East Asian (EAS) AF: 0.397 AC: 15605 AN: 39258

South Asian (SAS) AF: 0.130 AC: 11059 AN: 84834

European-Finnish (FIN) AF: 0.112 AC: 5735 AN: 51422

Middle Eastern (MID) AF: 0.0986 AC: 557 AN: 5648

European-Non Finnish (NFE) AF: 0.0999 AC: 105417 AN: 1055178

Other (OTH) AF: 0.125 AC: 7266 AN: 58314

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

African (AFR) AF: 0.155 AC: 6444 AN: 41444

American (AMR) AF: 0.120 AC: 1836 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1904 AN: 5166

South Asian (SAS) AF: 0.138 AC: 664 AN: 4812

European-Finnish (FIN) AF: 0.116 AC: 1224 AN: 10572

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0973 AC: 6595 AN: 67814

Other (OTH) AF: 0.114 AC: 240 AN: 2110

Alfa AF: 0.109 Hom.: 191

Bravo AF: 0.131

Asia WGS AF: 0.211 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.26
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

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