Variant 5-353740-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001377236.1(AHRR):c.73G>A(p.Val25Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000783 in 1,609,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

AHRR
NM_001377236.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.358

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04421705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AHRR	NM_001377236.1 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	3/11	ENST00000684583.1
PDCD6-AHRR	NR_165159.2 linkuse as main transcript	n.366G>A		non_coding_transcript_exon_variant	5/14
AHRR	NM_001377239.1 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	3/11
PDCD6-AHRR	NR_165163.2 linkuse as main transcript	n.366G>A		non_coding_transcript_exon_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHRR	ENST00000684583.1 linkuse as main transcript	c.73G>A	p.Val25Met	missense_variant	3/11		NM_001377236.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000613

AC:

AN:

244562

Hom.:

AF XY:

0.0000901

AC XY:

AN XY:

133182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000986

Gnomad FIN exome

AF:

0.0000499

Gnomad NFE exome

AF:

0.0000993

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000768

AC:

112

AN:

1457510

Hom.:

Cov.:

AF XY:

0.0000827

AC XY:

AN XY:

725104

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:

0.0000930

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.0000873

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.85G>A (p.V29M) alteration is located in exon 3 (coding exon 3) of the AHRR gene. This alteration results from a G to A substitution at nucleotide position 85, causing the valine (V) at amino acid position 29 to be replaced by a methionine (M). 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

0.077

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.31

DANN

Benign

0.83

DEOGEN2

Benign

0.065

T;.;.;.;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.12

T;T;T;T;T

M_CAP

Benign

0.0010

MetaRNN

Benign

0.044

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.50

N;N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.22

T;T;T;T;T

Sift4G

Benign

0.10

.;.;T;T;T

Polyphen

0.089

B;B;.;.;.

Vest4

0.20

MVP

0.24

MPC

0.64

ClinPred

0.063

GERP RS

-9.0

Varity_R

0.023

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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