chr16-10910293-C-T

Variant names:

• chr16-10910293-C-T
• rs4781019
• NM_000246.4:c.2888+34C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001286402.1(CIITA):​c.2891+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_001286402.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0120
• Publications: 14 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)

ENSG00000308110 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1184689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286402.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	NM_000246.4	MANE Select	c.2888+34C>T		intron	N/A	NP_000237.2
	CIITA	NM_001286402.1		c.2891+34C>T		intron	N/A	NP_001273331.1
	CIITA	NM_001379332.1		c.2891+34C>T		intron	N/A	NP_001366261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000324288.14	TSL:1 MANE Select	c.2888+34C>T		intron	N/A	ENSP00000316328.8
	CIITA	ENST00000381835.9	TSL:1	c.1136+34C>T		intron	N/A	ENSP00000371257.5
	CIITA	ENST00000886127.1		c.2891+34C>T		intron	N/A	ENSP00000556186.1

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

GnomAD2 exomes AF: 0.485 AC: 117413 AN: 242124 AF XY: 0.493

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 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

African (AFR) AF: 0.404 AC: 13292 AN: 32908

American (AMR) AF: 0.330 AC: 14483 AN: 43930

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 13129 AN: 25918

East Asian (EAS) AF: 0.341 AC: 13436 AN: 39372

South Asian (SAS) AF: 0.465 AC: 39564 AN: 85058

European-Finnish (FIN) AF: 0.528 AC: 27902 AN: 52890

Middle Eastern (MID) AF: 0.501 AC: 2871 AN: 5736

European-Non Finnish (NFE) AF: 0.567 AC: 619602 AN: 1092260

Other (OTH) AF: 0.519 AC: 30867 AN: 59504

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

African (AFR) AF: 0.399 AC: 16568 AN: 41476

American (AMR) AF: 0.426 AC: 6512 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1827 AN: 3468

East Asian (EAS) AF: 0.370 AC: 1911 AN: 5160

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4822

European-Finnish (FIN) AF: 0.534 AC: 5645 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38044 AN: 67974

Other (OTH) AF: 0.503 AC: 1063 AN: 2114

Alfa AF: 0.532 Hom.: 14560

Bravo AF: 0.473

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class II deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.78
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4781019; hg19: chr16-11004150;