7-17342116-T-C

Variant names:

• chr7-17342116-T-C
• rs2106728
• NM_001621.5:c.2404-805T>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.2404-805T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,046 control chromosomes in the GnomAD database, including 7,086 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 0.27 (7086 hom., cov: 32)
• Consequence: AHR NM_001621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.2404-805T>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.2404-805T>C		intron_variant	Intron 10 of 10	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.2373+1888T>C		intron_variant	Intron 10 of 11	5		ENSP00000490530.1
AHR	ENST00000463496.1	n.2404-805T>C		intron_variant	Intron 10 of 11	1		ENSP00000436466.1
AHR	ENST00000642825.1	c.2359-805T>C		intron_variant	Intron 14 of 14			ENSP00000495987.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41280 AN: 151928 Hom.: 7090 Cov.: 32

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.271 AC: 41261 AN: 152046 Hom.: 7086 Cov.: 32 AF XY: 0.270 AC XY: 20025 AN XY: 74300

African (AFR) AF: 0.0710 AC: 2949 AN: 41544

American (AMR) AF: 0.232 AC: 3543 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1043 AN: 5188

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4826

European-Finnish (FIN) AF: 0.413 AC: 4357 AN: 10560

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.389 AC: 26426 AN: 67882

Other (OTH) AF: 0.294 AC: 620 AN: 2110

Alfa AF: 0.356 Hom.: 11523

Bravo AF: 0.253

Asia WGS AF: 0.183 AC: 632 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.24
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: rs2106728; hg19: chr7-17381740;