16-10888488-G-C

Position:

• chr16-10888488-G-C

Variant summary

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

The NM_000246.4(CIITA):​c.53-6794G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,146 control chromosomes in the GnomAD database, including 8,969 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 0.33 (8969 hom., cov: 33)
  • Exomes 𝑓: 0.23 (0 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	NM_000246.4	c.53-6794G>C		intron_variant		ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14	c.53-6794G>C		intron_variant		1	NM_000246.4	ENSP00000316328.8

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49533 AN: 152004 Hom.: 8933 Cov.: 33

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.214

GnomAD4 genome AF: 0.326 AC: 49625 AN: 152124 Hom.: 8969 Cov.: 33 AF XY: 0.324 AC XY: 24126 AN XY: 74374

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.312

Alfa AF: 0.171 Hom.: 332

Bravo AF: 0.327

Asia WGS AF: 0.418 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8043545; hg19: chr16-10982345;