16-10874479-T-C

Variant summary

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

The ENST00000572017.1(ENSG00000262151):n.439-9429A>G 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 0.336 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: ENST00000572017.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIITA	XM_006720880.4	c.346+7907T>C		intron_variant
CIITA	XM_011522484.4	c.346+7907T>C		intron_variant
CIITA	XM_011522485.3	c.346+7907T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000572017.1	n.439-9429A>G		intron_variant, non_coding_transcript_variant		3
CIITA	ENST00000636238.1	c.-21+8160T>C		intron_variant		5
CIITA	ENST00000637439.1	c.283+7907T>C		intron_variant		5

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.877

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.340

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.1
Dann	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11074932; hg19: chr16-10968336;