ENST00000637439.1:c.283+3689G>T

Variant names:

• chr16-10870261-G-T
• rs6498114
• ENST00000637439.1:c.283+3689G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637439.1(CIITA):​c.283+3689G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 151,046 control chromosomes in the GnomAD database, including 45,709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45709 hom., cov: 27)
• Consequence: CIITA ENST00000637439.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 29 publications found

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]

CIITA Gene-Disease associations (from GenCC):

• MHC class II deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ENSG00000262151 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000637439.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000637439.1	TSL:5	c.283+3689G>T		intron	N/A	ENSP00000489907.1
	CIITA	ENST00000636238.1	TSL:5	c.-21+3942G>T		intron	N/A	ENSP00000490205.1
	ENSG00000262151	ENST00000572017.1	TSL:3	n.439-5211C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.773 AC: 116658 AN: 150930 Hom.: 45644 Cov.: 27

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.773 AC: 116779 AN: 151046 Hom.: 45709 Cov.: 27 AF XY: 0.769 AC XY: 56695 AN XY: 73692

African (AFR) AF: 0.869 AC: 35677 AN: 41052

American (AMR) AF: 0.804 AC: 12181 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2678 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2371 AN: 5134

South Asian (SAS) AF: 0.665 AC: 3183 AN: 4790

European-Finnish (FIN) AF: 0.716 AC: 7349 AN: 10266

Middle Eastern (MID) AF: 0.788 AC: 230 AN: 292

European-Non Finnish (NFE) AF: 0.748 AC: 50752 AN: 67890

Other (OTH) AF: 0.775 AC: 1625 AN: 2096

Alfa AF: 0.761 Hom.: 72410

Bravo AF: 0.788

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
DANN	Benign	0.46
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6498114; hg19: chr16-10964118;