Variant chr5-422840-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001377236.1(AHRR):c.553C>G(p.Pro185Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,612,388 control chromosomes in the GnomAD database, including 117,292 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.32 ( 8656 hom., cov: 32)

Exomes 𝑓: 0.38 ( 108636 hom. )

Consequence

AHRR
NM_001377236.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.914

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:):

PDCD6-AHRR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045746267).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AHRR	NM_001377236.1 linkuse as main transcript	c.553C>G	p.Pro185Ala	missense_variant	6/11	ENST00000684583.1
PDCD6-AHRR	NR_165159.2 linkuse as main transcript	n.846C>G		non_coding_transcript_exon_variant	8/14
AHRR	NM_001377239.1 linkuse as main transcript	c.553C>G	p.Pro185Ala	missense_variant	6/11
PDCD6-AHRR	NR_165163.2 linkuse as main transcript	n.846C>G		non_coding_transcript_exon_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
AHRR	ENST00000684583.1 linkuse as main transcript	c.553C>G	p.Pro185Ala	missense_variant	6/11		NM_001377236.1	P1
AHRR	ENST00000316418.10 linkuse as main transcript	c.553C>G	p.Pro185Ala	missense_variant	6/11	1		P1
AHRR	ENST00000506456.1 linkuse as main transcript	c.133C>G	p.Pro45Ala	missense_variant	2/7	2
AHRR	ENST00000510910.1 linkuse as main transcript	n.464C>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48390

AN:

151996

Hom.:

8660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.283

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.375

AC:

93047

AN:

248018

Hom.:

18525

AF XY:

0.387

AC XY:

52153

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.254

Gnomad ASJ exome

AF:

0.430

Gnomad EAS exome

AF:

0.395

Gnomad SAS exome

AF:

0.450

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.399

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.381

AC:

556402

AN:

1460274

Hom.:

108636

Cov.:

AF XY:

0.385

AC XY:

279507

AN XY:

726198

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.436

Gnomad4 EAS exome

AF:

0.390

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.449

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.318

AC:

48383

AN:

152114

Hom.:

8656

Cov.:

AF XY:

0.325

AC XY:

24178

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.283

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.387

Gnomad4 SAS

AF:

0.439

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.349

Hom.:

3107

Bravo

AF:

0.298

TwinsUK

AF:

0.374

AC:

1386

ALSPAC

AF:

0.366

AC:

1409

ESP6500AA

AF:

0.147

AC:

593

ESP6500EA

AF:

0.378

AC:

3154

ExAC

AF:

0.377

AC:

45620

Asia WGS

AF:

0.416

AC:

1446

AN:

3478

EpiCase

AF:

0.391

EpiControl

AF:

0.389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.088

T;.;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.51

T;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

M;M;.;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.072

T;T;T;T

Sift4G

Benign

0.41

.;.;T;T

Polyphen

0.067

B;B;.;P

Vest4

0.17

MPC

0.63

ClinPred

0.028

GERP RS

3.1

Varity_R

0.044

gMVP

0.22

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over