16-10916787-C-T

Variant names:

• chr16-10916787-C-T
• rs6498132
• NM_000246.4:c.3062+328C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000246.4(CIITA):​c.3062+328C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 430,092 control chromosomes in the GnomAD database, including 4,877 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 0.14 (1862 hom., cov: 33)
  • Exomes 𝑓: 0.13 (3015 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4	c.3062+328C>T		intron_variant	Intron 15 of 19	ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14	c.3062+328C>T		intron_variant	Intron 15 of 19	1	NM_000246.4	ENSP00000316328.8

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21613 AN: 152130 Hom.: 1850 Cov.: 33

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.133 AC: 36893 AN: 277844 Hom.: 3015 Cov.: 0 AF XY: 0.129 AC XY: 18561 AN XY: 143894

African (AFR) AF: 0.155 AC: 1450 AN: 9360

American (AMR) AF: 0.335 AC: 3823 AN: 11420

Ashkenazi Jewish (ASJ) AF: 0.0780 AC: 768 AN: 9848

East Asian (EAS) AF: 0.196 AC: 3840 AN: 19558

South Asian (SAS) AF: 0.122 AC: 4556 AN: 37250

European-Finnish (FIN) AF: 0.110 AC: 1072 AN: 9772

Middle Eastern (MID) AF: 0.137 AC: 167 AN: 1216

European-Non Finnish (NFE) AF: 0.116 AC: 18954 AN: 162868

Other (OTH) AF: 0.137 AC: 2263 AN: 16552

GnomAD4 genome AF: 0.142 AC: 21653 AN: 152248 Hom.: 1862 Cov.: 33 AF XY: 0.145 AC XY: 10815 AN XY: 74450

African (AFR) AF: 0.152 AC: 6317 AN: 41530

American (AMR) AF: 0.271 AC: 4147 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3470

East Asian (EAS) AF: 0.146 AC: 757 AN: 5182

South Asian (SAS) AF: 0.131 AC: 631 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10614

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7976 AN: 68024

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.158 Hom.: 473

Bravo AF: 0.158

Asia WGS AF: 0.205 AC: 714 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	0.12
DANN	Benign	0.68
PhyloP100		-0.31
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: rs6498132; hg19: chr16-11010644;