rs10499480

chr7-17076408-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643090.1(ENSG00000237773):n.307-104662T>C variant causes a intron, non coding transcript 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: ENST00000643090.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893

Genes affected

(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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LOC124901596	XR_007060240.1	n.472-9990T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000643090.1	n.307-104662T>C		intron_variant, non_coding_transcript_variant
AHR	ENST00000645559.1	n.31-128295A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.302

Alfa AF: 0.319 Hom.: 3866

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10499480; hg19: chr7-17116032;