rs4436808

Positions:

• chr16-10868709-G-A
• chr16-10868709-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637439.1(CIITA):​c.283+2137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 152,138 control chromosomes in the GnomAD database, including 1,025 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 0.050 (1025 hom., cov: 32)
• Consequence: CIITA ENST00000637439.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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]

ENSG00000262151 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	XM_006720880.4	c.346+2137G>A		intron_variant			XP_006720943.2
CIITA	XM_011522484.4	c.346+2137G>A		intron_variant			XP_011520786.1
CIITA	XM_011522485.3	c.346+2137G>A		intron_variant			XP_011520787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000637439.1	c.283+2137G>A		intron_variant		5		ENSP00000489907.1
CIITA	ENST00000636238.1	c.-21+2390G>A		intron_variant		5		ENSP00000490205.1
ENSG00000262151	ENST00000572017.1	n.439-3659C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0500 AC: 7607 AN: 152020 Hom.: 1014 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.0802

Gnomad FIN AF: 0.0276

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0501 AC: 7622 AN: 152138 Hom.: 1025 Cov.: 32 AF XY: 0.0583 AC XY: 4339 AN XY: 74366

Gnomad4 AFR AF: 0.0106

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.0801

Gnomad4 FIN AF: 0.0276

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0536

Alfa AF: 0.0104 Hom.: 11

Bravo AF: 0.0725

Asia WGS AF: 0.142 AC: 495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.91
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4436808; hg19: chr16-10962566;