ENST00000637439.1:c.283+8043C>T

Variant names:

• chr16-10874615-C-T
• rs9302456
• ENST00000637439.1:c.283+8043C>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+8043C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,160 control chromosomes in the GnomAD database, including 6,102 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 0.26 (6102 hom., cov: 32)
• Consequence: CIITA ENST00000637439.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 4 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	XM_006720880.4	c.346+8043C>T		intron_variant	Intron 1 of 19		XP_006720943.2
CIITA	XM_011522484.4	c.346+8043C>T		intron_variant	Intron 1 of 19		XP_011520786.1
CIITA	XM_011522485.3	c.346+8043C>T		intron_variant	Intron 1 of 19		XP_011520787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000637439.1	c.283+8043C>T		intron_variant	Intron 1 of 6	5		ENSP00000489907.1
CIITA	ENST00000636238.1	c.-21+8296C>T		intron_variant	Intron 1 of 5	5		ENSP00000490205.1
ENSG00000262151	ENST00000572017.1	n.439-9565G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39448 AN: 152042 Hom.: 6103 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.259 AC: 39452 AN: 152160 Hom.: 6102 Cov.: 32 AF XY: 0.261 AC XY: 19383 AN XY: 74382

African (AFR) AF: 0.110 AC: 4588 AN: 41526

American (AMR) AF: 0.222 AC: 3392 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 1209 AN: 3472

East Asian (EAS) AF: 0.0853 AC: 442 AN: 5184

South Asian (SAS) AF: 0.369 AC: 1777 AN: 4812

European-Finnish (FIN) AF: 0.361 AC: 3822 AN: 10576

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23062 AN: 67992

Other (OTH) AF: 0.288 AC: 610 AN: 2116

Alfa AF: 0.306 Hom.: 9099

Bravo AF: 0.239

Asia WGS AF: 0.253 AC: 880 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.53
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs9302456; hg19: chr16-10968472;