rs10499480

Variant names:

• chr7-17076408-A-G
• rs10499480
• ENST00000643090.1:n.307-104662T>C

Variant summary

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

The ENST00000643090.1(ENSG00000237773):​n.307-104662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,844 control chromosomes in the GnomAD database, including 6,000 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 0.26 (6000 hom., cov: 31)
• Consequence: ENSG00000237773 ENST00000643090.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124901596	XR_007060240.1	n.472-9990T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000237773	ENST00000643090.1	n.307-104662T>C		intron_variant	Intron 2 of 2
AHR	ENST00000645559.1	n.31-128295A>G		intron_variant	Intron 1 of 1
ENSG00000289189	ENST00000766378.1	n.278-17084A>G		intron_variant	Intron 1 of 1
ENSG00000289189	ENST00000766379.1	n.61-7435A>G		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39536 AN: 151724 Hom.: 5998 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.260 AC: 39546 AN: 151844 Hom.: 6000 Cov.: 31 AF XY: 0.258 AC XY: 19128 AN XY: 74224

African (AFR) AF: 0.113 AC: 4701 AN: 41518

American (AMR) AF: 0.243 AC: 3710 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1509 AN: 3456

East Asian (EAS) AF: 0.296 AC: 1534 AN: 5174

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2524 AN: 10574

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22827 AN: 67748

Other (OTH) AF: 0.302 AC: 639 AN: 2114

Alfa AF: 0.318 Hom.: 4319

Bravo AF: 0.252

Asia WGS AF: 0.311 AC: 1081 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.91
PhyloP100		0.89

Splicing

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

Other links and lift over

dbSNP: rs10499480; hg19: chr7-17116032;