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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643090.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000237773	ENST00000643090.1		n.307-104662T>C		intron	N/A
	AHR	ENST00000645559.1		n.31-128295A>G		intron	N/A
	ENSG00000289189	ENST00000766378.1		n.278-17084A>G		intron	N/A

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10499480;

hg19: chr7-17116032;