rs45474796
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000246.4(CIITA):c.200-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,614,120 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0061 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0098 ( 99 hom. )
Consequence
CIITA
NM_000246.4 splice_polypyrimidine_tract, intron
NM_000246.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0006234
2
Clinical Significance
Conservation
PhyloP100: 2.13
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 16-10895659-T-C is Benign according to our data. Variant chr16-10895659-T-C is described in ClinVar as [Benign]. Clinvar id is 317676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-10895659-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00611 (931/152272) while in subpopulation SAS AF= 0.0139 (67/4826). AF 95% confidence interval is 0.0112. There are 3 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIITA | NM_000246.4 | c.200-10T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000324288.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIITA | ENST00000324288.14 | c.200-10T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000246.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00609 AC: 926AN: 152154Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00897 AC: 2255AN: 251456Hom.: 16 AF XY: 0.00938 AC XY: 1275AN XY: 135900
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GnomAD4 exome AF: 0.00976 AC: 14270AN: 1461848Hom.: 99 Cov.: 32 AF XY: 0.0101 AC XY: 7379AN XY: 727232
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GnomAD4 genome ? AF: 0.00611 AC: 931AN: 152272Hom.: 3 Cov.: 32 AF XY: 0.00637 AC XY: 474AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MHC class II deficiency Benign:3
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at