16-10870261-G-T

Position:

• chr16-10870261-G-T

Variant summary

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

The ENST00000572017.1(ENSG00000262151):​n.439-5211C>A 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 0.773 in 151,046 control chromosomes in the GnomAD database, including 45,709 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 0.77 (45709 hom., cov: 27)
• Consequence: ENST00000572017.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CIITA	XM_006720880.4	c.346+3689G>T		intron_variant
CIITA	XM_011522484.4	c.346+3689G>T		intron_variant
CIITA	XM_011522485.3	c.346+3689G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000572017.1	n.439-5211C>A		intron_variant, non_coding_transcript_variant		3
CIITA	ENST00000636238.1	c.-21+3942G>T		intron_variant		5
CIITA	ENST00000637439.1	c.283+3689G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.773 AC: 116658 AN: 150930 Hom.: 45644 Cov.: 27

Gnomad AFR AF: 0.869

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.773 AC: 116779 AN: 151046 Hom.: 45709 Cov.: 27 AF XY: 0.769 AC XY: 56695 AN XY: 73692

Gnomad4 AFR AF: 0.869

Gnomad4 AMR AF: 0.804

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.716

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.775

Alfa AF: 0.755 Hom.: 53791

Bravo AF: 0.788

Asia WGS AF: 0.637 AC: 2217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.089
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6498114; hg19: chr16-10964118;