NM_001621.5:c.254-1604T>C

Variant names:

• chr7-17320897-T-C
• rs17137566
• NM_001621.5:c.254-1604T>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.254-1604T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,072 control chromosomes in the GnomAD database, including 2,523 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 0.18 (2523 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.254-1604T>C		intron_variant	Intron 2 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.254-1604T>C		intron_variant	Intron 2 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.224-1604T>C		intron_variant	Intron 2 of 11	5		ENSP00000490530.1
AHR	ENST00000463496.1	n.254-1604T>C		intron_variant	Intron 2 of 11	1		ENSP00000436466.1
AHR	ENST00000642825.1	c.209-1604T>C		intron_variant	Intron 6 of 14			ENSP00000495987.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26831 AN: 151952 Hom.: 2524 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.176 AC: 26840 AN: 152072 Hom.: 2523 Cov.: 32 AF XY: 0.178 AC XY: 13211 AN XY: 74338

African (AFR) AF: 0.168 AC: 6958 AN: 41514

American (AMR) AF: 0.164 AC: 2505 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.392 AC: 2026 AN: 5168

South Asian (SAS) AF: 0.177 AC: 854 AN: 4818

European-Finnish (FIN) AF: 0.160 AC: 1691 AN: 10592

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11733 AN: 67934

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.170 Hom.: 6278

Bravo AF: 0.179

Asia WGS AF: 0.230 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		-0.54
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: rs17137566; hg19: chr7-17360521;