ENST00000642825.1:c.20+1899C>T

Variant names:

• chr7-17298523-C-T
• rs10249788
• ENST00000642825.1:c.20+1899C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642825.1(AHR):​c.20+1899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 316,128 control chromosomes in the GnomAD database, including 7,455 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 0.23 (4389 hom., cov: 21)
  • Exomes 𝑓: 0.16 (3066 hom.)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 25 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

ENSG00000237773 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642825.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	NM_001621.5	MANE Select	c.-742C>T		upstream_gene	N/A	NP_001612.1	P35869

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000642825.1		c.20+1899C>T		intron	N/A	ENSP00000495987.1	A0A2R8Y7G1
	ENSG00000237773	ENST00000659284.2		n.13G>A		non_coding_transcript_exon	Exon 1 of 5
	ENSG00000237773	ENST00000838557.1		n.2G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.230 AC: 30732 AN: 133798 Hom.: 4366 Cov.: 21

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.162 AC: 29575 AN: 182264 Hom.: 3066 Cov.: 0 AF XY: 0.160 AC XY: 14859 AN XY: 92628

African (AFR) AF: 0.387 AC: 2016 AN: 5214

American (AMR) AF: 0.331 AC: 1730 AN: 5230

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 843 AN: 7146

East Asian (EAS) AF: 0.319 AC: 5330 AN: 16720

South Asian (SAS) AF: 0.203 AC: 331 AN: 1632

European-Finnish (FIN) AF: 0.116 AC: 1793 AN: 15402

Middle Eastern (MID) AF: 0.133 AC: 128 AN: 964

European-Non Finnish (NFE) AF: 0.129 AC: 15218 AN: 117768

Other (OTH) AF: 0.179 AC: 2186 AN: 12188

GnomAD4 genome AF: 0.230 AC: 30805 AN: 133864 Hom.: 4389 Cov.: 21 AF XY: 0.235 AC XY: 14993 AN XY: 63902

African (AFR) AF: 0.398 AC: 14033 AN: 35288

American (AMR) AF: 0.321 AC: 4096 AN: 12750

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 423 AN: 3306

East Asian (EAS) AF: 0.276 AC: 1198 AN: 4348

South Asian (SAS) AF: 0.214 AC: 868 AN: 4058

European-Finnish (FIN) AF: 0.146 AC: 1094 AN: 7510

Middle Eastern (MID) AF: 0.137 AC: 32 AN: 234

European-Non Finnish (NFE) AF: 0.135 AC: 8599 AN: 63690

Other (OTH) AF: 0.203 AC: 373 AN: 1834

Alfa AF: 0.139 Hom.: 1061

Bravo AF: 0.241

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.6
DANN	Benign	0.95
PhyloP100		-1.6
PromoterAI		-0.24	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10249788; hg19: chr7-17338147;