rs4781010

Variant names:

• chr16-10876601-T-A
• rs4781010
• ENST00000637439.1:c.283+10029T>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10876601-T-A
• chr16-10876601-T-G

Variant summary

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

The ENST00000637439.1(CIITA):​c.283+10029T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 152,142 control chromosomes in the GnomAD database, including 1,099 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 0.051 (1099 hom., cov: 33)
• Consequence: CIITA ENST00000637439.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644
• Publications: 0 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)

ENSG00000262151 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	XM_006720880.4	c.346+10029T>A		intron_variant	Intron 1 of 19		XP_006720943.2
CIITA	XM_011522484.4	c.346+10029T>A		intron_variant	Intron 1 of 19		XP_011520786.1
CIITA	XM_011522485.3	c.346+10029T>A		intron_variant	Intron 1 of 19		XP_011520787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000637439.1	c.283+10029T>A		intron_variant	Intron 1 of 6	5		ENSP00000489907.1
CIITA	ENST00000636238.1	c.-21+10282T>A		intron_variant	Intron 1 of 5	5		ENSP00000490205.1
ENSG00000262151	ENST00000572017.1	n.439-11551A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7758 AN: 152022 Hom.: 1086 Cov.: 33

Gnomad AFR AF: 0.00901

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.00895

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0511 AC: 7775 AN: 152142 Hom.: 1099 Cov.: 33 AF XY: 0.0596 AC XY: 4431 AN XY: 74360

African (AFR) AF: 0.00899 AC: 373 AN: 41512

American (AMR) AF: 0.278 AC: 4237 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00895 AC: 31 AN: 3464

East Asian (EAS) AF: 0.301 AC: 1560 AN: 5180

South Asian (SAS) AF: 0.0814 AC: 391 AN: 4806

European-Finnish (FIN) AF: 0.0280 AC: 296 AN: 10588

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 771 AN: 68008

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.00895 Hom.: 2

Bravo AF: 0.0742

Asia WGS AF: 0.158 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.3
DANN	Benign	0.85
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs4781010; hg19: chr16-10970458;