rs1139564

Variant names:

• chr16-10924765-T-C
• rs1139564
• NM_000246.4:c.*910T>C

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.*910T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,242 control chromosomes in the GnomAD database, including 40,940 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40924 hom., cov: 34)
  • Exomes 𝑓: 0.83 (16 hom.)
• Consequence: CIITA NM_001286402.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.19
• Publications: 16 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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-10924765-T-C is Benign according to our data. Variant chr16-10924765-T-C is described in ClinVar as Benign. ClinVar VariationId is 317747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.809 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	NM_000246.4	MANE Select	c.*910T>C		3_prime_UTR	Exon 20 of 20	NP_000237.2
	CIITA	NM_001286402.1		c.*910T>C		3_prime_UTR	Exon 20 of 20	NP_001273331.1
	CIITA	NM_001286403.2		c.*910T>C		3_prime_UTR	Exon 18 of 18	NP_001273332.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000324288.14	TSL:1 MANE Select	c.*910T>C		3_prime_UTR	Exon 20 of 20	ENSP00000316328.8
	CIITA	ENST00000886127.1		c.*910T>C		3_prime_UTR	Exon 21 of 21	ENSP00000556186.1
	CIITA	ENST00000618327.4	TSL:2	c.*910T>C		3_prime_UTR	Exon 20 of 20	ENSP00000485010.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109218 AN: 152082 Hom.: 40904 Cov.: 34

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 0.833 AC: 35 AN: 42 Hom.: 16 Cov.: 0 AF XY: 0.875 AC XY: 21 AN XY: 24

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 8 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.808 AC: 21 AN: 26

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.718 AC: 109282 AN: 152200 Hom.: 40924 Cov.: 34 AF XY: 0.720 AC XY: 53594 AN XY: 74414

African (AFR) AF: 0.481 AC: 19952 AN: 41496

American (AMR) AF: 0.785 AC: 12022 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2817 AN: 3472

East Asian (EAS) AF: 0.761 AC: 3938 AN: 5176

South Asian (SAS) AF: 0.741 AC: 3578 AN: 4830

European-Finnish (FIN) AF: 0.864 AC: 9147 AN: 10590

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55375 AN: 68012

Other (OTH) AF: 0.725 AC: 1532 AN: 2112

Alfa AF: 0.777 Hom.: 43194

Bravo AF: 0.702

Asia WGS AF: 0.742 AC: 2578 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	-0.89
CADD	Benign	0.56
DANN	Benign	0.56
PhyloP100		-1.2
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: rs1139564; hg19: chr16-11018622;