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GeneBe

5-422791-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001377236.1(AHRR):c.504C>T(p.Cys168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00789 in 1,614,134 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0072 ( 90 hom. )

Consequence

AHRR
NM_001377236.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.180
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-422791-C-T is Benign according to our data. Variant chr5-422791-C-T is described in ClinVar as [Benign]. Clinvar id is 778862.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.18 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0149 (2271/152304) while in subpopulation AFR AF= 0.0407 (1693/41558). AF 95% confidence interval is 0.0391. There are 36 homozygotes in gnomad4. There are 1066 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AHRRNM_001377236.1 linkuse as main transcriptc.504C>T p.Cys168= synonymous_variant 6/11 ENST00000684583.1
PDCD6-AHRRNR_165159.2 linkuse as main transcriptn.797C>T non_coding_transcript_exon_variant 8/14
AHRRNM_001377239.1 linkuse as main transcriptc.504C>T p.Cys168= synonymous_variant 6/11
PDCD6-AHRRNR_165163.2 linkuse as main transcriptn.797C>T non_coding_transcript_exon_variant 8/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHRRENST00000684583.1 linkuse as main transcriptc.504C>T p.Cys168= synonymous_variant 6/11 NM_001377236.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0149
AC:
2270
AN:
152186
Hom.:
38
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0409
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00582
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0122
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00591
Gnomad OTH
AF:
0.00764
GnomAD3 exomes
AF:
0.00753
AC:
1879
AN:
249434
Hom.:
33
AF XY:
0.00747
AC XY:
1011
AN XY:
135366
show subpopulations
Gnomad AFR exome
AF:
0.0447
Gnomad AMR exome
AF:
0.00356
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.0125
Gnomad FIN exome
AF:
0.000742
Gnomad NFE exome
AF:
0.00551
Gnomad OTH exome
AF:
0.00578
GnomAD4 exome
AF:
0.00716
AC:
10465
AN:
1461830
Hom.:
90
Cov.:
30
AF XY:
0.00714
AC XY:
5194
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0431
Gnomad4 AMR exome
AF:
0.00389
Gnomad4 ASJ exome
AF:
0.000536
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0137
Gnomad4 FIN exome
AF:
0.000899
Gnomad4 NFE exome
AF:
0.00643
Gnomad4 OTH exome
AF:
0.00685
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0149
AC:
2271
AN:
152304
Hom.:
36
Cov.:
32
AF XY:
0.0143
AC XY:
1066
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0407
Gnomad4 AMR
AF:
0.00581
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0122
Gnomad4 FIN
AF:
0.000753
Gnomad4 NFE
AF:
0.00591
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00946
Hom.:
9
Bravo
AF:
0.0175
Asia WGS
AF:
0.0120
AC:
43
AN:
3478
EpiCase
AF:
0.00589
EpiControl
AF:
0.00581

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.41
Cadd
Benign
11
Dann
Benign
0.83

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.

Other links and lift over

dbSNP: rs61755969; hg19: chr5-422906; API