16-10874479-T-C

Variant names:

• chr16-10874479-T-C
• rs11074932
• ENST00000637439.1:c.283+7907T>C

Variant summary

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

The ENST00000572017.1(ENSG00000262151):​n.439-9429A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,020 control chromosomes in the GnomAD database, including 9,969 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 0.34 (9969 hom., cov: 32)
• Consequence: ENSG00000262151 ENST00000572017.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283
• Publications: 6 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000262151 (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 (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572017.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000637439.1	TSL:5	c.283+7907T>C		intron	N/A	ENSP00000489907.1	A0A1B0GU01
	CIITA	ENST00000636238.1	TSL:5	c.-21+8160T>C		intron	N/A	ENSP00000490205.1	A0A1B0GUQ8
	ENSG00000262151	ENST00000572017.1	TSL:3	n.439-9429A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51030 AN: 151902 Hom.: 9958 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.877

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.336 AC: 51065 AN: 152020 Hom.: 9969 Cov.: 32 AF XY: 0.346 AC XY: 25730 AN XY: 74286

African (AFR) AF: 0.257 AC: 10647 AN: 41462

American (AMR) AF: 0.511 AC: 7798 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1007 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4532 AN: 5168

South Asian (SAS) AF: 0.450 AC: 2162 AN: 4808

European-Finnish (FIN) AF: 0.333 AC: 3512 AN: 10562

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20406 AN: 67976

Other (OTH) AF: 0.340 AC: 715 AN: 2106

Alfa AF: 0.307 Hom.: 949

Bravo AF: 0.348

Asia WGS AF: 0.581 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11074932; hg19: chr16-10968336;