Genetic Variant AHRR:p.Pro185Ser (chr5-422840-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001377236.1(AHRR):c.553C>T(p.Pro185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

AHRR
NM_001377236.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.914

Publications

64 publications found

Variant links:

Genes affected

AHRR (HGNC:346): (aryl hydrocarbon receptor repressor) The protein encoded by this gene participates in the aryl hydrocarbon receptor (AhR) signaling cascade, which mediates dioxin toxicity, and is involved in regulation of cell growth and differentiation. It functions as a feedback modulator by repressing AhR-dependent gene expression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

AHRR links:

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDCD6-AHRR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09926185).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377236.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AHRR	NM_001377236.1	MANE Select	c.553C>T	p.Pro185Ser	missense	Exon 6 of 11	NP_001364165.1	A0A7I2PK40
AHRR	NM_001377239.1		c.553C>T	p.Pro185Ser	missense	Exon 6 of 11	NP_001364168.1	A0A7I2PK40
PDCD6-AHRR	NR_165159.2		n.846C>T		non_coding_transcript_exon	Exon 8 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AHRR	ENST00000684583.1	MANE Select	c.553C>T	p.Pro185Ser	missense	Exon 6 of 11	ENSP00000507476.1	A0A7I2PK40
AHRR	ENST00000316418.10	TSL:1	c.553C>T	p.Pro185Ser	missense	Exon 6 of 11	ENSP00000323816.6	A0A7I2PK40
PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*549C>T		non_coding_transcript_exon	Exon 8 of 13	ENSP00000424601.2	A0A6Q8PH81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248018

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000137

AC:

AN:

1460454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726298

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111140

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

3107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.079

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.61

M_CAP

Benign

0.0043

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.91

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.9

REVEL

Benign

0.037

Sift

Benign

0.29

Sift4G

Benign

0.41

Polyphen

0.067

Vest4

0.17

MutPred

0.36

Loss of glycosylation at P190 (P = 0.063)

MVP

0.37

MPC

0.83

ClinPred

0.28

GERP RS

3.1

Varity_R

0.041

gMVP

0.27

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over