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GeneBe

5-413406-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001377236.1(AHRR):c.414G>A(p.Thr138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 1,613,802 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00090 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

AHRR
NM_001377236.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.42
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 -11 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=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-413406-G-A is Benign according to our data. Variant chr5-413406-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655243.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=-2.42 with no splicing effect.
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 GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AHRRNM_001377236.1 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 5/11 ENST00000684583.1
PDCD6-AHRRNR_165159.2 linkuse as main transcriptn.707G>A non_coding_transcript_exon_variant 7/14
AHRRNM_001377239.1 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 5/11
PDCD6-AHRRNR_165163.2 linkuse as main transcriptn.707G>A non_coding_transcript_exon_variant 7/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AHRRENST00000684583.1 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 5/11 NM_001377236.1 P1
AHRRENST00000316418.10 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 5/111 P1
AHRRENST00000510400.5 linkuse as main transcriptc.414G>A p.Thr138= synonymous_variant 5/64
AHRRENST00000514523.1 linkuse as main transcriptc.-37G>A 5_prime_UTR_variant 5/64

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000901
AC:
137
AN:
152058
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000197
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00166
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000910
AC:
227
AN:
249406
Hom.:
2
AF XY:
0.000968
AC XY:
131
AN XY:
135318
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000589
Gnomad FIN exome
AF:
0.00209
Gnomad NFE exome
AF:
0.00138
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00138
AC:
2013
AN:
1461626
Hom.:
3
Cov.:
31
AF XY:
0.00135
AC XY:
978
AN XY:
727118
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000557
Gnomad4 FIN exome
AF:
0.00183
Gnomad4 NFE exome
AF:
0.00162
Gnomad4 OTH exome
AF:
0.000795
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000900
AC:
137
AN:
152176
Hom.:
1
Cov.:
32
AF XY:
0.000927
AC XY:
69
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.00166
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000869
Hom.:
0
Bravo
AF:
0.000801
EpiCase
AF:
0.00115
EpiControl
AF:
0.00124

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2022AHRR: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
1.6
Dann
Benign
0.80

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: rs188075736; hg19: chr5-413521; API