rs11074938

Positions:

• chr16-10912686-A-G
• chr16-10912686-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000246.4(CIITA):​c.2888+2427A>G variant causes a intron change. The variant allele was found at a frequency of 0.559 in 152,076 control chromosomes in the GnomAD database, including 24,189 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 0.56 (24189 hom., cov: 33)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIITA	NM_000246.4	c.2888+2427A>G		intron_variant		ENST00000324288.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CIITA	ENST00000324288.14	c.2888+2427A>G		intron_variant		1	NM_000246.4	P4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84931 AN: 151960 Hom.: 24175 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.559 AC: 84977 AN: 152076 Hom.: 24189 Cov.: 33 AF XY: 0.559 AC XY: 41597 AN XY: 74356

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.524

Alfa AF: 0.561 Hom.: 21712

Bravo AF: 0.532

Asia WGS AF: 0.564 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.93

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: rs11074938; hg19: chr16-11006543;