rs2066853

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001621.5(AHR):c.1661G>A(p.Arg554Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,866 control chromosomes in the GnomAD database, including 20,829 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 (★★). Synonymous variant affecting the same amino acid position (i.e. R554R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.22 ( 5364 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15465 hom. )

Consequence

AHR
NM_001621.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.65

Publications

191 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014748573).

BP6

Variant 7-17339486-G-A is Benign according to our data. Variant chr7-17339486-G-A is described in ClinVar as Benign. ClinVar VariationId is 1168239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5 link	c.1661G>A	p.Arg554Lys	missense_variant	Exon 10 of 11	ENST00000242057.9	NP_001612.1	P35869A0A024R9Z8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9 link	c.1661G>A	p.Arg554Lys	missense_variant	Exon 10 of 11	1	NM_001621.5	ENSP00000242057.4		P35869
ENSG00000283321	ENST00000637807.1 link	c.1631G>A	p.Arg544Lys	missense_variant	Exon 10 of 12	5		ENSP00000490530.1		A0A1B0GVI7

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32840

AN:

151982

Hom.:

5335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.176

GnomAD2 exomes

AF:

0.152

AC:

38185

AN:

250730

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.458

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.141

GnomAD4 exome

AF:

0.126

AC:

183916

AN:

1461766

Hom.:

15465

Cov.:

AF XY:

0.125

AC XY:

90675

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.460

AC:

15410

AN:

33472

American (AMR)

AF:

0.133

AC:

5948

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3230

AN:

26130

East Asian (EAS)

AF:

0.402

AC:

15934

AN:

39682

South Asian (SAS)

AF:

0.137

AC:

11853

AN:

86242

European-Finnish (FIN)

AF:

0.112

AC:

5953

AN:

53384

Middle Eastern (MID)

AF:

0.151

AC:

870

AN:

5768

European-Non Finnish (NFE)

AF:

0.104

AC:

115583

AN:

1111984

Other (OTH)

AF:

0.151

AC:

9135

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

9616

19233

28849

38466

48082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4652

9304

13956

18608

23260

<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:

0.216

AC:

32915

AN:

152100

Hom.:

5364

Cov.:

AF XY:

0.216

AC XY:

16058

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.452

AC:

18745

AN:

41446

American (AMR)

AF:

0.155

AC:

2366

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

444

AN:

3472

East Asian (EAS)

AF:

0.377

AC:

1952

AN:

5174

South Asian (SAS)

AF:

0.145

AC:

697

AN:

4822

European-Finnish (FIN)

AF:

0.115

AC:

1222

AN:

10586

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

6978

AN:

67996

Other (OTH)

AF:

0.175

AC:

369

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1174

2348

3521

4695

5869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.141

Hom.:

9049

Bravo

AF:

0.231

TwinsUK

AF:

0.105

AC:

389

ALSPAC

AF:

0.116

AC:

447

ESP6500AA

AF:

0.444

AC:

1957

ESP6500EA

AF:

0.101

AC:

870

ExAC

AF:

0.157

AC:

18996

Asia WGS

AF:

0.237

AC:

822

AN:

3478

EpiCase

AF:

0.103

EpiControl

AF:

0.0986

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 22, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29185192, 10739168, 21454829, 21742528, 18818557) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.8

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.079

.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.41

T;.;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.5

.;N;.

PhyloP100

1.7

PrimateAI

Benign

0.27

PROVEAN

Benign

1.2

.;N;.

REVEL

Benign

0.040

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

.;T;.

Polyphen

0.0

.;B;.

Vest4

0.0050

MPC

0.11

ClinPred

0.0014

GERP RS

0.60

Varity_R

0.035

gMVP

0.13

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