Genetic Variant AHR:c.-202-9863T>C (chr7-17286434-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000642825.1(AHR):c.-202-9863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,020 control chromosomes in the GnomAD database, including 9,373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 9373 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

AHR
ENST00000642825.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.152

Publications

6 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:

ENSG00000237773 (HGNC:):

ENSG00000237773 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000642825.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642825.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHR	ENST00000642825.1		c.-202-9863T>C	intron	N/A	ENSP00000495987.1	A0A2R8Y7G1
ENSG00000237773	ENST00000415246.3	TSL:3	n.492A>G	non_coding_transcript_exon	Exon 4 of 4
ENSG00000237773	ENST00000419382.7	TSL:3	n.237A>G	non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48089

AN:

151902

Hom.:

9336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.298

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.317

AC:

48188

AN:

152020

Hom.:

9373

Cov.:

AF XY:

0.314

AC XY:

23363

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.544

AC:

22551

AN:

41434

American (AMR)

AF:

0.351

AC:

5357

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

581

AN:

3468

East Asian (EAS)

AF:

0.273

AC:

1414

AN:

5182

South Asian (SAS)

AF:

0.249

AC:

1201

AN:

4816

European-Finnish (FIN)

AF:

0.157

AC:

1665

AN:

10572

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14575

AN:

67952

Other (OTH)

AF:

0.295

AC:

623

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1524

3048

4572

6096

7620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.242

Hom.:

7212

Bravo

AF:

0.344

Asia WGS

AF:

0.263

AC:

912

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.1

(source)

DANN

Benign

0.69

PhyloP100

-0.15

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over