Genetic Variant NM_001377236.1:c.76G>C (chr5-353743-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001377236.1(AHRR):c.76G>C(p.Gly26Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000891 in 1,458,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

AHRR
NM_001377236.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.56

Publications

0 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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38598493).

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.76G>C	p.Gly26Arg	missense	Exon 3 of 11	NP_001364165.1	A0A7I2PK40
AHRR	NM_001377239.1		c.76G>C	p.Gly26Arg	missense	Exon 3 of 11	NP_001364168.1	A0A7I2PK40
PDCD6-AHRR	NR_165159.2		n.369G>C		non_coding_transcript_exon	Exon 5 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AHRR	ENST00000684583.1	MANE Select	c.76G>C	p.Gly26Arg	missense	Exon 3 of 11	ENSP00000507476.1	A0A7I2PK40
AHRR	ENST00000316418.10	TSL:1	c.76G>C	p.Gly26Arg	missense	Exon 3 of 11	ENSP00000323816.6	A0A7I2PK40
PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*72G>C		non_coding_transcript_exon	Exon 5 of 13	ENSP00000424601.2	A0A6Q8PH81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458282

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725524

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26016

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5560

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111244

Other (OTH)

AF:

0.00

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

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:

0.0000472

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

M_CAP

Benign

0.011

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.28

PhyloP100

6.6

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.21

Sift

Uncertain

0.0070

Sift4G

Benign

0.078

Polyphen

1.0

Vest4

0.40

MutPred

0.26

Loss of loop (P = 0.0203)

MVP

0.65

MPC

1.7

ClinPred

0.91

GERP RS

4.5

Varity_R

0.22

gMVP

0.49

Mutation Taster

=46/54

disease causing

(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