Genetic Variant ENST00000642825.1:c.-202-2932C>T (chr7-17293365-C-T) – 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.-202-2932C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 151,948 control chromosomes in the GnomAD database, including 47,564 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 0.79 ( 47564 hom., cov: 30)

Consequence

AHR
ENST00000642825.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

10 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:

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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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC101927609	XR_007060230.1 link	n.220+1801G>A	intron_variant	Intron 2 of 5
LOC101927609	XR_007060231.1 link	n.220+1801G>A	intron_variant	Intron 2 of 4
LOC101927609	XR_007060232.1 link	n.220+1801G>A	intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
AHR	ENST00000642825.1 link	c.-202-2932C>T	intron_variant	Intron 3 of 14		ENSP00000495987.1	A0A2R8Y7G1
ENSG00000237773	ENST00000415246.3 link	n.267+1801G>A	intron_variant	Intron 2 of 3	3
ENSG00000237773	ENST00000419382.7 link	n.154+4987G>A	intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119581

AN:

151830

Hom.:

47530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.752

Gnomad EAS

AF:

0.632

Gnomad SAS

AF:

0.716

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.750

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.788

AC:

119669

AN:

151948

Hom.:

47564

Cov.:

AF XY:

0.785

AC XY:

58308

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.893

AC:

37025

AN:

41464

American (AMR)

AF:

0.698

AC:

10646

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.752

AC:

2610

AN:

3470

East Asian (EAS)

AF:

0.632

AC:

3262

AN:

5162

South Asian (SAS)

AF:

0.715

AC:

3449

AN:

4822

European-Finnish (FIN)

AF:

0.797

AC:

8409

AN:

10546

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.761

AC:

51684

AN:

67914

Other (OTH)

AF:

0.780

AC:

1644

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1275

2551

3826

5102

6377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.765

Hom.:

50588

Bravo

AF:

0.786

Asia WGS

AF:

0.682

AC:

2371

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.0

(source)

DANN

Benign

0.66

PhyloP100

0.016

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over