rs4781024
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000246.4(CIITA):c.3318-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,607,398 control chromosomes in the GnomAD database, including 122,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.34 ( 9427 hom., cov: 32)
Exomes 𝑓: 0.39 ( 112952 hom. )
Consequence
CIITA
NM_000246.4 intron
NM_000246.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.591
Genes affected
CIITA (HGNC:7067): (class II major histocompatibility complex transactivator) This gene encodes a protein with an acidic transcriptional activation domain, 4 LRRs (leucine-rich repeats) and a GTP binding domain. The protein is located in the nucleus and acts as a positive regulator of class II major histocompatibility complex gene transcription, and is referred to as the "master control factor" for the expression of these genes. The protein also binds GTP and uses GTP binding to facilitate its own transport into the nucleus. Once in the nucleus it does not bind DNA but rather uses an intrinsic acetyltransferase (AT) activity to act in a coactivator-like fashion. Mutations in this gene have been associated with bare lymphocyte syndrome type II (also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency), increased susceptibility to rheumatoid arthritis, multiple sclerosis, and possibly myocardial infarction. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 16-10923201-G-A is Benign according to our data. Variant chr16-10923201-G-A is described in ClinVar as [Benign]. Clinvar id is 1184692.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.3318-27G>A | intron_variant | ENST00000324288.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.3318-27G>A | intron_variant | 1 | NM_000246.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.341 AC: 51807AN: 151932Hom.: 9427 Cov.: 32
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GnomAD3 exomes AF: 0.367 AC: 91103AN: 248480Hom.: 17806 AF XY: 0.378 AC XY: 50914AN XY: 134516
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GnomAD4 exome AF: 0.390 AC: 566944AN: 1455346Hom.: 112952 Cov.: 31 AF XY: 0.392 AC XY: 283706AN XY: 724262
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GnomAD4 genome ? AF: 0.341 AC: 51814AN: 152052Hom.: 9427 Cov.: 32 AF XY: 0.339 AC XY: 25165AN XY: 74336
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MHC class II deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at