rs4719497

Variant names:

• chr7-17295275-T-C
• rs4719497
• ENST00000654641.1:n.2034A>G

Variant summary

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

The ENST00000654641.1(ENSG00000237773):​n.2034A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 152,234 control chromosomes in the GnomAD database, including 997 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 0.097 (997 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000237773 ENST00000654641.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 20 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060230.1	n.113-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 5
LOC101927609	XR_007060231.1	n.113-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 4
LOC101927609	XR_007060232.1	n.113-2A>G		splice_acceptor_variant, intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000654641.1	n.2034A>G		non_coding_transcript_exon_variant	Exon 1 of 3
ENSG00000237773	ENST00000665788.1	n.2051A>G		non_coding_transcript_exon_variant	Exon 1 of 2
AHR	ENST00000642825.1	c.-202-1022T>C		intron_variant	Intron 3 of 14			ENSP00000495987.1

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14696 AN: 152116 Hom.: 999 Cov.: 31

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0966

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0965 AC: 14695 AN: 152234 Hom.: 997 Cov.: 31 AF XY: 0.0948 AC XY: 7060 AN XY: 74438

African (AFR) AF: 0.0248 AC: 1031 AN: 41568

American (AMR) AF: 0.145 AC: 2224 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3468

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5186

South Asian (SAS) AF: 0.0610 AC: 294 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1092 AN: 10610

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9480 AN: 67974

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.120 Hom.: 2138

Bravo AF: 0.0964

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.83
PhyloP100		-0.0030
Mutation Taster		=74/26	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4719497; hg19: chr7-17334899;