7-17323944-C-T

Variant names:

• chr7-17323944-C-T
• rs4236290
• NM_001621.5:c.360+1337C>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.360+1337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,238 control chromosomes in the GnomAD database, including 63,121 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 0.91 (63121 hom., cov: 31)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.360+1337C>T		intron_variant	Intron 3 of 10	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.360+1337C>T		intron_variant	Intron 3 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.330+1337C>T		intron_variant	Intron 3 of 11	5		ENSP00000490530.1
AHR	ENST00000463496.1	n.360+1337C>T		intron_variant	Intron 3 of 11	1		ENSP00000436466.1
AHR	ENST00000642825.1	c.315+1337C>T		intron_variant	Intron 7 of 14			ENSP00000495987.1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138240 AN: 152120 Hom.: 63074 Cov.: 31

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.909 AC: 138340 AN: 152238 Hom.: 63121 Cov.: 31 AF XY: 0.910 AC XY: 67718 AN XY: 74414

African (AFR) AF: 0.976 AC: 40565 AN: 41552

American (AMR) AF: 0.804 AC: 12258 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3023 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5168 AN: 5178

South Asian (SAS) AF: 0.912 AC: 4403 AN: 4830

European-Finnish (FIN) AF: 0.937 AC: 9949 AN: 10616

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60030 AN: 68020

Other (OTH) AF: 0.902 AC: 1904 AN: 2112

Alfa AF: 0.885 Hom.: 109700

Bravo AF: 0.901

Asia WGS AF: 0.949 AC: 3294 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4236290; hg19: chr7-17363568;