7-17309937-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001621.5(AHR):c.67G>A(p.Val23Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000255 in 1,567,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

AHR
NM_001621.5 missense, splice_region

Scores

Splicing: ADA: 0.003163

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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 links:

ENSG00000283321 (HGNC:):

ENSG00000283321 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12345639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5 link	c.67G>A	p.Val23Ile	missense_variant, splice_region_variant	Exon 2 of 11	ENST00000242057.9	NP_001612.1	P35869A0A024R9Z8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
AHR	ENST00000242057.9 link	c.67G>A	p.Val23Ile	missense_variant, splice_region_variant	Exon 2 of 11	1	NM_001621.5	ENSP00000242057.4	P35869
ENSG00000283321	ENST00000637807.1 link	c.37G>A	p.Val13Ile	missense_variant, splice_region_variant	Exon 2 of 12	5		ENSP00000490530.1	A0A1B0GVI7
AHR	ENST00000463496.1 link	n.67G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 12	1		ENSP00000436466.1	P35869
AHR	ENST00000642825.1 link	c.22G>A	p.Val8Ile	missense_variant, splice_region_variant	Exon 6 of 15			ENSP00000495987.1	A0A2R8Y7G1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247562

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133768

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1415076

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700428

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.26e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.67G>A (p.V23I) alteration is located in exon 2 (coding exon 2) of the AHR gene. This alteration results from a G to A substitution at nucleotide position 67, causing the valine (V) at amino acid position 23 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

0.010

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.24

T;.;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.92

.;L;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.67

.;N;.

REVEL

Benign

0.021

Sift

Benign

0.18

.;T;.

Sift4G

Benign

0.58

.;T;.

Polyphen

0.0030

.;B;.

Vest4

0.086

MVP

0.26

MPC

0.093

ClinPred

0.27

GERP RS

4.8

Varity_R

0.068

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0032

dbscSNV1_RF

Benign

0.13

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over