rs3087456

Positions:

• chr16-10877045-G-A
• chr16-10877045-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000572017.1(ENSG00000262151):​n.438+11270C>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 0.528 in 152,140 control chromosomes in the GnomAD database, including 26,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.53 (26202 hom., cov: 32)
• Consequence: ENST00000572017.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0920

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 16-10877045-G-A is Benign according to our data. Variant chr16-10877045-G-A is described in ClinVar as [Benign]. Clinvar id is 1168170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	XM_006720880.4	c.346+10473G>A		intron_variant			XP_006720943.2
CIITA	XM_011522484.4	c.346+10473G>A		intron_variant			XP_011520786.1
CIITA	XM_011522485.3	c.346+10473G>A		intron_variant			XP_011520787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000572017.1	n.438+11270C>T		intron_variant, non_coding_transcript_variant		3
CIITA	ENST00000636238.1	c.-21+10726G>A		intron_variant		5		ENSP00000490205
CIITA	ENST00000637439.1	c.283+10473G>A		intron_variant		5		ENSP00000489907

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80420 AN: 152022 Hom.: 26211 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.731

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.528 AC: 80403 AN: 152140 Hom.: 26202 Cov.: 32 AF XY: 0.525 AC XY: 39022 AN XY: 74388

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.731

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.574

Alfa AF: 0.700 Hom.: 28318

Bravo AF: 0.490

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

MHC class II deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3087456; hg19: chr16-10970902;