rs4781020

Variant names:

• chr16-10914405-G-A
• rs4781020
• NM_000246.4:c.2889-1165G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10914405-G-A
• chr16-10914405-G-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.2889-1165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,064 control chromosomes in the GnomAD database, including 4,805 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 0.23 (4805 hom., cov: 32)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• 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 (SAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000246.4. 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.2889-1165G>A		intron	N/A	NP_000237.2
	CIITA	NM_001286402.1		c.2892-1165G>A		intron	N/A	NP_001273331.1
	CIITA	NM_001379332.1		c.2892-1165G>A		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.2889-1165G>A		intron	N/A	ENSP00000316328.8
	CIITA	ENST00000381835.9	TSL:1	c.1137-1165G>A		intron	N/A	ENSP00000371257.5
	CIITA	ENST00000618327.4	TSL:2	c.2892-1165G>A		intron	N/A	ENSP00000485010.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35586 AN: 151946 Hom.: 4805 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.234 AC: 35594 AN: 152064 Hom.: 4805 Cov.: 32 AF XY: 0.236 AC XY: 17544 AN XY: 74312

African (AFR) AF: 0.0901 AC: 3738 AN: 41502

American (AMR) AF: 0.207 AC: 3156 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1702 AN: 5172

South Asian (SAS) AF: 0.369 AC: 1782 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3156 AN: 10556

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19806 AN: 67968

Other (OTH) AF: 0.240 AC: 505 AN: 2108

Alfa AF: 0.227 Hom.: 1651

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.66
PhyloP100		-0.60
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: rs4781020; hg19: chr16-11008262;