rs4986826

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001621.5(AHR):c.1708G>A(p.Val570Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 1,614,096 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V570A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.021 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 114 hom. )

Consequence

AHR
NM_001621.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.49

Publications

29 publications found

Variant links:

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]

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

AHR links:

ENSG00000283321 (HGNC:):

ENSG00000283321 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021272004).

BP6

Variant 7-17339533-G-A is Benign according to our data. Variant chr7-17339533-G-A is described in ClinVar as Benign. ClinVar VariationId is 780672.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5 link	c.1708G>A	p.Val570Ile	missense_variant	Exon 10 of 11	ENST00000242057.9	NP_001612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9 link	c.1708G>A	p.Val570Ile	missense_variant	Exon 10 of 11	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1 link	c.1678G>A	p.Val560Ile	missense_variant	Exon 10 of 12	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes

AF:

0.0213

AC:

3247

AN:

152156

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.00220

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.00779

AC:

1956

AN:

251078

AF XY:

0.00649

show subpopulations

Gnomad AFR exome

AF:

0.0701

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00913

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.00388

AC:

5670

AN:

1461822

Hom.:

114

Cov.:

AF XY:

0.00366

AC XY:

2665

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.0709

AC:

2374

AN:

33478

American (AMR)

AF:

0.0109

AC:

488

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0103

AC:

268

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00152

AC:

131

AN:

86248

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.0394

AC:

227

AN:

5768

European-Non Finnish (NFE)

AF:

0.00148

AC:

1641

AN:

1112000

Other (OTH)

AF:

0.00892

AC:

539

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

339

678

1017

1356

1695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0214

AC:

3264

AN:

152274

Hom.:

115

Cov.:

AF XY:

0.0208

AC XY:

1546

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0679

AC:

2819

AN:

41546

American (AMR)

AF:

0.0127

AC:

195

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00220

AC:

150

AN:

68028

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

152

304

456

608

760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00936

Hom.:

Bravo

AF:

0.0241

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0647

AC:

285

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00867

AC:

1052

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00421

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

AHR-related disorder

Benign:1

Feb 17, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.80

T;.;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L;.

PhyloP100

1.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.28

.;N;.

REVEL

Benign

0.062

Sift

Benign

0.42

.;T;.

Sift4G

Benign

0.41

.;T;.

Polyphen

0.30

.;B;.

Vest4

0.028

MVP

0.38

MPC

0.090

ClinPred

0.0089

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over