7-17310002-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001621.5(AHR):c.132T>C(p.Asn44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 1,613,268 control chromosomes in the GnomAD database, including 5,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (447 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5386 hom.)
• Consequence: AHR NM_001621.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.669

Genes affected

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-17310002-T-C is Benign according to our data. Variant chr7-17310002-T-C is described in ClinVar as [Benign]. Clinvar id is 1166758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.669 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHR	NM_001621.5	c.132T>C	p.Asn44=	synonymous_variant	2/11	ENST00000242057.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHR	ENST00000242057.9	c.132T>C	p.Asn44=	synonymous_variant	2/11	1	NM_001621.5	P2
AHR	ENST00000463496.1	c.132T>C	p.Asn44=	synonymous_variant, NMD_transcript_variant	2/12	1
AHR	ENST00000642825.1	c.87T>C	p.Asn29=	synonymous_variant	6/15			A2

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10357 AN: 152126 Hom.: 447 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0335

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0569

GnomAD3 exomes AF: 0.0771 AC: 19364 AN: 251286 Hom.: 891 AF XY: 0.0810 AC XY: 10996 AN XY: 135808

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.0311

Gnomad ASJ exome AF: 0.0373

Gnomad EAS exome AF: 0.0357

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.0870

Gnomad OTH exome AF: 0.0747

GnomAD4 exome AF: 0.0817 AC: 119372 AN: 1461024 Hom.: 5386 Cov.: 31 AF XY: 0.0832 AC XY: 60453 AN XY: 726796

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.0337

Gnomad4 SAS exome AF: 0.107

Gnomad4 FIN exome AF: 0.144

Gnomad4 NFE exome AF: 0.0836

Gnomad4 OTH exome AF: 0.0728

GnomAD4 genome AF: 0.0680 AC: 10347 AN: 152244 Hom.: 447 Cov.: 32 AF XY: 0.0706 AC XY: 5253 AN XY: 74438

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0343

Gnomad4 EAS AF: 0.0332

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0796 Hom.: 1213

Bravo AF: 0.0563

Asia WGS AF: 0.0790 AC: 272 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

AHR-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.4
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs17779352; hg19: chr7-17349626; COSMIC: COSV54126865;