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rs2066853

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

12

Clinical Significance

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

Conservation

PhyloP100: 1.65
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons MANE UniProt
AHRNM_001621.5 linkuse as main transcriptc.1661G>A p.Arg554Lys missense_variant 10/11 ENST00000242057.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHRENST00000242057.9 linkuse as main transcriptc.1661G>A p.Arg554Lys missense_variant 10/111 NM_001621.5 P2
AHRENST00000463496.1 linkuse as main transcriptc.1661G>A p.Arg554Lys missense_variant, NMD_transcript_variant 10/121
AHRENST00000642825.1 linkuse as main transcriptc.1616G>A p.Arg539Lys missense_variant 14/15 A2
AHRENST00000492120.1 linkuse as main transcriptn.643G>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.216
AC:
32840
AN:
151982
Hom.:
5335
Cov.:
32
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
GnomAD3 exomes
AF:
0.152
AC:
38185
AN:
250730
Hom.:
4212
AF XY:
0.144
AC XY:
19600
AN XY:
135698
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 SAS exome
AF:
0.137
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.:
33
AF XY:
0.125
AC XY:
90675
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.460
Gnomad4 AMR exome
AF:
0.133
Gnomad4 ASJ exome
AF:
0.124
Gnomad4 EAS exome
AF:
0.402
Gnomad4 SAS exome
AF:
0.137
Gnomad4 FIN exome
AF:
0.112
Gnomad4 NFE exome
AF:
0.104
Gnomad4 OTH exome
AF:
0.151
GnomAD4 genome
AF:
0.216
AC:
32915
AN:
152100
Hom.:
5364
Cov.:
32
AF XY:
0.216
AC XY:
16058
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.452
Gnomad4 AMR
AF:
0.155
Gnomad4 ASJ
AF:
0.128
Gnomad4 EAS
AF:
0.377
Gnomad4 SAS
AF:
0.145
Gnomad4 FIN
AF:
0.115
Gnomad4 NFE
AF:
0.103
Gnomad4 OTH
AF:
0.175
Alfa
AF:
0.122
Hom.:
4045
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
Benign, criteria provided, single submitterclinical testingGeneDxAug 22, 2019This variant is associated with the following publications: (PMID: 29185192, 10739168, 21454829, 21742528, 18818557) -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.79
Cadd
Benign
4.8
Dann
Benign
0.55
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.41
T;.;T
MetaRNN
Benign
0.0015
T;T;T
MetaSVM
Benign
-0.90
T
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.27
T
Polyphen
0.0
.;B;.
Vest4
0.0050
MPC
0.11
ClinPred
0.0014
T
GERP RS
0.60
Varity_R
0.035
gMVP
0.13

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2066853; hg19: chr7-17379110; COSMIC: COSV54123264; COSMIC: COSV54123264; API