rs4781019

chr16-10910293-C-T

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.2888+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,589,638 control chromosomes in the GnomAD database, including 230,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18638 hom., cov: 32)
  • Exomes 𝑓: 0.54 (211812 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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=-0.81).
• BP6: Variant 16-10910293-C-T is Benign according to our data. Variant chr16-10910293-C-T is described in ClinVar as [Benign]. Clinvar id is 1184689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIITA	NM_000246.4	c.2888+34C>T		intron_variant		ENST00000324288.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIITA	ENST00000324288.14	c.2888+34C>T		intron_variant		1	NM_000246.4	P4

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74300 AN: 151944 Hom.: 18635 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.503

GnomAD3 exomes AF: 0.485 AC: 117413 AN: 242124 Hom.: 29233 AF XY: 0.493 AC XY: 64564 AN XY: 130868

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.461

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.562

Gnomad OTH exome AF: 0.511

GnomAD4 exome AF: 0.539 AC: 775146 AN: 1437576 Hom.: 211812 Cov.: 26 AF XY: 0.538 AC XY: 385397 AN XY: 715978

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.528

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.519

GnomAD4 genome AF: 0.489 AC: 74335 AN: 152062 Hom.: 18638 Cov.: 32 AF XY: 0.485 AC XY: 36055 AN XY: 74316

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.503

Alfa AF: 0.534 Hom.: 12926

Bravo AF: 0.473

Asia WGS AF: 0.425 AC: 1477 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	-0.81
Cadd	Benign	6.4
Dann	Benign	0.78

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: rs4781019; hg19: chr16-11004150;