rs3087456

Variant names:

• chr16-10877045-G-A
• rs3087456
• ENST00000637439.1:c.283+10473G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000572017.1(ENSG00000262151):​n.438+11270C>T variant causes a intron 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: ENSG00000262151 ENST00000572017.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0920
• Publications: 61 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000262151 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572017.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	NM_000246.4	MANE Select	c.-286G>A		upstream_gene	N/A	NP_000237.2
	CIITA	NM_001286402.1		c.-286G>A		upstream_gene	N/A	NP_001273331.1	A0A087X2I7
	CIITA	NM_001379332.1		c.-286G>A		upstream_gene	N/A	NP_001366261.1	A0A087X2I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000637439.1	TSL:5	c.283+10473G>A		intron	N/A	ENSP00000489907.1	A0A1B0GU01
	CIITA	ENST00000636238.1	TSL:5	c.-21+10726G>A		intron	N/A	ENSP00000490205.1	A0A1B0GUQ8
	ENSG00000262151	ENST00000572017.1	TSL:3	n.438+11270C>T		intron	N/A

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

African (AFR) AF: 0.180 AC: 7488 AN: 41494

American (AMR) AF: 0.471 AC: 7206 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.732 AC: 2540 AN: 3468

East Asian (EAS) AF: 0.121 AC: 625 AN: 5186

South Asian (SAS) AF: 0.568 AC: 2738 AN: 4818

European-Finnish (FIN) AF: 0.731 AC: 7741 AN: 10584

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.734 AC: 49924 AN: 67974

Other (OTH) AF: 0.574 AC: 1212 AN: 2110

Alfa AF: 0.669 Hom.: 36158

Bravo AF: 0.490

Asia WGS AF: 0.377 AC: 1314 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	MHC class II deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.76
PhyloP100		0.092
PromoterAI		-0.091	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3087456; hg19: chr16-10970902;