Variant chr5-343937-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001377236.1(AHRR):c.35G>A(p.Arg12Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,600,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AHRR
NM_001377236.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.69

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AHRR	NM_001377236.1 link	c.35G>A	p.Arg12Gln	missense_variant	2/11	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1 link	c.35G>A	p.Arg12Gln	missense_variant	2/11		NP_001364168.1
PDCD6-AHRR	NR_165159.2 link	n.328G>A		non_coding_transcript_exon_variant	4/14
PDCD6-AHRR	NR_165163.2 link	n.328G>A		non_coding_transcript_exon_variant	4/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	ENST00000684583.1 link	c.35G>A	p.Arg12Gln	missense_variant	2/11	NM_001377236.1	ENSP00000507476.1	A0A7I2PK40
PDCD6-AHRR	ENST00000675395.1 link	n.*31G>A		non_coding_transcript_exon_variant	4/14		ENSP00000502570.1	A0A6Q8PH81
PDCD6-AHRR	ENST00000675395.1 link	n.*31G>A		3_prime_UTR_variant	4/14		ENSP00000502570.1	A0A6Q8PH81

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1448944

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720948

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74112

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jul 05, 2024

The c.47G>A (p.R16Q) alteration is located in exon 2 (coding exon 2) of the AHRR gene. This alteration results from a G to A substitution at nucleotide position 47, causing the arginine (R) at amino acid position 16 to be replaced by a glutamine (Q). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;.;.;.;.

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.43

T;T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.9

L;L;.;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Benign

0.26

Sift

Uncertain

0.019

D;D;D;D;D

Sift4G

Uncertain

0.036

.;.;D;D;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.41

MutPred

0.22

Loss of MoRF binding (P = 0.0452);Loss of MoRF binding (P = 0.0452);.;.;.;

MVP

0.82

MPC

1.7

ClinPred

0.90

GERP RS

4.4

Varity_R

0.25

gMVP

0.68

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over