chr21-44290023-C-G
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000383.4(AIRE):c.834C>G(p.Ser278Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,610,112 control chromosomes in the GnomAD database, including 14,899 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S278S) has been classified as Likely benign.
Frequency
Consequence
NM_000383.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AIRE | NM_000383.4 | c.834C>G | p.Ser278Arg | missense_variant | 7/14 | ENST00000291582.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AIRE | ENST00000291582.6 | c.834C>G | p.Ser278Arg | missense_variant | 7/14 | 1 | NM_000383.4 | P1 | |
AIRE | ENST00000527919.5 | n.1567C>G | non_coding_transcript_exon_variant | 7/14 | 2 | ||||
AIRE | ENST00000530812.5 | n.2584C>G | non_coding_transcript_exon_variant | 5/12 | 2 |
Frequencies
GnomAD3 genomes AF: 0.164 AC: 24937AN: 152018Hom.: 2704 Cov.: 33
GnomAD3 exomes AF: 0.142 AC: 34231AN: 240646Hom.: 3317 AF XY: 0.140 AC XY: 18469AN XY: 131566
GnomAD4 exome AF: 0.115 AC: 168045AN: 1457976Hom.: 12188 Cov.: 34 AF XY: 0.116 AC XY: 84324AN XY: 725244
GnomAD4 genome AF: 0.164 AC: 24974AN: 152136Hom.: 2711 Cov.: 33 AF XY: 0.166 AC XY: 12382AN XY: 74388
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 14, 2014 | - - |
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, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. - |
Polyglandular autoimmune syndrome, type 1 Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | This variant is associated with the following publications: (PMID: 21505073, 19322061, 25525159, 12542742) - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 11, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at