chr5-427664-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001377236.1(AHRR):c.709-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,754 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: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
AHRR
NM_001377236.1 intron
NM_001377236.1 intron
Scores
1
13
Clinical Significance
Conservation
PhyloP100: -1.26
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12965524).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AHRR | NM_001377236.1 | c.709-143C>T | intron_variant | ENST00000684583.1 | |||
PDCD6-AHRR | NR_165159.2 | n.1029C>T | non_coding_transcript_exon_variant | 10/14 | |||
AHRR | NM_001377239.1 | c.709-143C>T | intron_variant | ||||
PDCD6-AHRR | NR_165163.2 | n.1002-143C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AHRR | ENST00000684583.1 | c.709-143C>T | intron_variant | NM_001377236.1 | P1 | ||||
AHRR | ENST00000316418.10 | c.709-143C>T | intron_variant | 1 | P1 | ||||
AHRR | ENST00000506456.1 | c.289-143C>T | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247496Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134860
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460754Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726704
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GnomAD4 genome ? Cov.: 34
GnomAD4 genome
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Cov.:
34
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 | Dec 27, 2023 | The c.748C>T (p.R250W) alteration is located in exon 8 (coding exon 8) of the AHRR gene. This alteration results from a C to T substitution at nucleotide position 748, causing the arginine (R) at amino acid position 250 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.0676);
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at