rs4781010

chr16-10876601-T-Achr16-10876601-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572017.1(ENSG00000262151):n.439-11551A>T variant causes a intron, non coding transcript 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: ENST00000572017.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

Genes affected

(HGNC:):

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 -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/exons	MANE	UniProt
CIITA	XM_006720880.4	c.346+10029T>A		intron_variant
CIITA	XM_011522484.4	c.346+10029T>A		intron_variant
CIITA	XM_011522485.3	c.346+10029T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000572017.1	n.439-11551A>T		intron_variant, non_coding_transcript_variant		3
CIITA	ENST00000636238.1	c.-21+10282T>A		intron_variant		5
CIITA	ENST00000637439.1	c.283+10029T>A		intron_variant		5

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

Gnomad4 AFR AF: 0.00899

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.00895

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.0814

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.0530

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4781010; hg19: chr16-10970458;