7-16976071-G-T

Variant names:

• chr7-16976071-G-T
• rs1523635
• ENST00000643090.1:n.307-4325C>A

Variant summary

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

The ENST00000643090.1(ENSG00000237773):​n.307-4325C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,962 control chromosomes in the GnomAD database, including 6,233 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 (6233 hom., cov: 31)
• Consequence: ENSG00000237773 ENST00000643090.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889
• Publications: 7 publications found

Genes affected

ENSG00000237773 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000643090.1	n.307-4325C>A		intron_variant	Intron 2 of 2
AHR	ENST00000645559.1	n.30+59683G>T		intron_variant	Intron 1 of 1
ENSG00000289189	ENST00000766377.1	n.342-36378G>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40578 AN: 151844 Hom.: 6224 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.267 AC: 40604 AN: 151962 Hom.: 6233 Cov.: 31 AF XY: 0.273 AC XY: 20295 AN XY: 74258

African (AFR) AF: 0.149 AC: 6163 AN: 41478

American (AMR) AF: 0.354 AC: 5401 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 815 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3236 AN: 5148

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4808

European-Finnish (FIN) AF: 0.301 AC: 3180 AN: 10556

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19202 AN: 67954

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.278 Hom.: 25638

Bravo AF: 0.270

Asia WGS AF: 0.414 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.1
DANN	Benign	0.82
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs1523635; hg19: chr7-17015695;