16-10905816-C-G

Variant names:

• chr16-10905816-C-G
• rs7404615
• NM_000246.4:c.1007-683C>G

Variant summary

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

The NM_001286402.1(CIITA):​c.1010-683C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 151,946 control chromosomes in the GnomAD database, including 66,203 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 0.93 (66203 hom., cov: 29)
• Consequence: CIITA NM_001286402.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1007-683C>G		intron	N/A	NP_000237.2
	CIITA	NM_001286402.1		c.1010-683C>G		intron	N/A	NP_001273331.1
	CIITA	NM_001379332.1		c.1010-683C>G		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.1007-683C>G		intron	N/A	ENSP00000316328.8
	CIITA	ENST00000381835.9	TSL:1	c.859+1004C>G		intron	N/A	ENSP00000371257.5
	CIITA	ENST00000537380.1	TSL:1	n.1006+1004C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.927 AC: 140682 AN: 151830 Hom.: 66169 Cov.: 29

Gnomad AFR AF: 0.743

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.949

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.926 AC: 140770 AN: 151946 Hom.: 66203 Cov.: 29 AF XY: 0.929 AC XY: 68965 AN XY: 74258

African (AFR) AF: 0.743 AC: 30715 AN: 41342

American (AMR) AF: 0.975 AC: 14920 AN: 15296

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 0.999 AC: 4797 AN: 4802

European-Finnish (FIN) AF: 1.00 AC: 10574 AN: 10574

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67915 AN: 67974

Other (OTH) AF: 0.950 AC: 2006 AN: 2112

Alfa AF: 0.961 Hom.: 3473

Bravo AF: 0.915

Asia WGS AF: 0.987 AC: 3434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.47
DANN	Benign	0.23
PhyloP100		-0.51
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: rs7404615; hg19: chr16-10999673;