rs3746964
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000383.4(AIRE):āc.99T>Cā(p.Ala33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 1,546,618 control chromosomes in the GnomAD database, including 13,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.17 ( 5926 hom., cov: 32)
Exomes š: 0.042 ( 7454 hom. )
Consequence
AIRE
NM_000383.4 synonymous
NM_000383.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.36
Genes affected
AIRE (HGNC:360): (autoimmune regulator) This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 21-44286105-T-C is Benign according to our data. Variant chr21-44286105-T-C is described in ClinVar as [Benign]. Clinvar id is 35669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44286105-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-4.36 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIRE | NM_000383.4 | c.99T>C | p.Ala33= | synonymous_variant | 1/14 | ENST00000291582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.99T>C | p.Ala33= | synonymous_variant | 1/14 | 1 | NM_000383.4 | P1 | |
AIRE | ENST00000527919.5 | n.260T>C | non_coding_transcript_exon_variant | 1/14 | 2 | ||||
AIRE | ENST00000530812.5 | n.268T>C | non_coding_transcript_exon_variant | 1/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.174 AC: 26395AN: 151962Hom.: 5891 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
26395
AN:
151962
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0910 AC: 12890AN: 141686Hom.: 1730 AF XY: 0.0847 AC XY: 6508AN XY: 76840
GnomAD3 exomes
AF:
AC:
12890
AN:
141686
Hom.:
AF XY:
AC XY:
6508
AN XY:
76840
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0425 AC: 59241AN: 1394548Hom.: 7454 Cov.: 30 AF XY: 0.0425 AC XY: 29262AN XY: 688016
GnomAD4 exome
AF:
AC:
59241
AN:
1394548
Hom.:
Cov.:
30
AF XY:
AC XY:
29262
AN XY:
688016
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.174 AC: 26482AN: 152070Hom.: 5926 Cov.: 32 AF XY: 0.172 AC XY: 12768AN XY: 74346
GnomAD4 genome
?
AF:
AC:
26482
AN:
152070
Hom.:
Cov.:
32
AF XY:
AC XY:
12768
AN XY:
74346
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
657
AN:
3456
ClinVar
Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Polyglandular autoimmune syndrome, type 1 Benign:3
Benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 20, 2010 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 10, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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