rs2301677

Variant names:

• chr7-17286434-T-C
• rs2301677
• ENST00000415246.3:n.492A>G

Variant summary

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

The ENST00000415246.3(ENSG00000237773):​n.492A>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 0.317 in 152,020 control chromosomes in the GnomAD database, including 9,373 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 0.32 (9373 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000237773 ENST00000415246.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 6 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060230.1	n.445A>G		non_coding_transcript_exon_variant	Exon 4 of 6
LOC101927609	XR_007060231.1	n.303A>G		non_coding_transcript_exon_variant	Exon 3 of 5
LOC101927609	XR_007060232.1	n.303A>G		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000415246.3	n.492A>G		non_coding_transcript_exon_variant	Exon 4 of 4	3
ENSG00000237773	ENST00000419382.7	n.237A>G		non_coding_transcript_exon_variant	Exon 2 of 4	3
ENSG00000237773	ENST00000424101.6	n.282A>G		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48089 AN: 151902 Hom.: 9336 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.298

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: 0.317 AC: 48188 AN: 152020 Hom.: 9373 Cov.: 32 AF XY: 0.314 AC XY: 23363 AN XY: 74302

African (AFR) AF: 0.544 AC: 22551 AN: 41434

American (AMR) AF: 0.351 AC: 5357 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 581 AN: 3468

East Asian (EAS) AF: 0.273 AC: 1414 AN: 5182

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4816

European-Finnish (FIN) AF: 0.157 AC: 1665 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14575 AN: 67952

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.242 Hom.: 7212

Bravo AF: 0.344

Asia WGS AF: 0.263 AC: 912 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs2301677; hg19: chr7-17326058;