rs4781016

chr16-10902542-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000246.4(CIITA):c.629-116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,299,786 control chromosomes in the GnomAD database, including 52,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6092 hom., cov: 33)
  • Exomes 𝑓: 0.28 (46612 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-10902542-C-A is Benign according to our data. Variant chr16-10902542-C-A is described in ClinVar as [Benign]. Clinvar id is 1184677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIITA	NM_000246.4	c.629-116C>A		intron_variant		ENST00000324288.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIITA	ENST00000324288.14	c.629-116C>A		intron_variant		1	NM_000246.4	P4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42011 AN: 152034 Hom.: 6088 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.273

GnomAD4 exome AF: 0.278 AC: 319425 AN: 1147634 Hom.: 46612 AF XY: 0.276 AC XY: 160229 AN XY: 580694

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.209

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.276 AC: 42049 AN: 152152 Hom.: 6092 Cov.: 33 AF XY: 0.275 AC XY: 20458 AN XY: 74372

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.276

Alfa AF: 0.296 Hom.: 9442

Bravo AF: 0.289

Asia WGS AF: 0.257 AC: 894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MHC class II deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	12
Dann	Benign	0.54

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: rs4781016; hg19: chr16-10996399; COSMIC: COSV60861061; COSMIC: COSV60861061;