16-10929351-T-C

Variant names:

• chr16-10929351-T-C
• rs3087519
• NM_000246.4:c.*5496T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000246.4(CIITA):​c.*5496T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 985,642 control chromosomes in the GnomAD database, including 130,543 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 0.44 (16889 hom., cov: 32)
  • Exomes 𝑓: 0.52 (113654 hom.)
• Consequence: CIITA NM_000246.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 14 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]

DEXI (HGNC:13267): (Dexi homolog)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000246.4. 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.*5496T>C		3_prime_UTR	Exon 20 of 20	NP_000237.2
	DEXI	NM_014015.4	MANE Select	c.*358A>G		3_prime_UTR	Exon 2 of 2	NP_054734.2
	CIITA	NM_001286403.2		c.*5496T>C		3_prime_UTR	Exon 18 of 18	NP_001273332.1	P33076-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000324288.14	TSL:1 MANE Select	c.*5496T>C		3_prime_UTR	Exon 20 of 20	ENSP00000316328.8
	DEXI	ENST00000331808.5	TSL:1 MANE Select	c.*358A>G		3_prime_UTR	Exon 2 of 2	ENSP00000330509.4	O95424
	DEXI	ENST00000469379.5	TSL:2	c.*519A>G		3_prime_UTR	Exon 3 of 3	ENSP00000482265.1	O95424

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67643 AN: 151952 Hom.: 16894 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.520 AC: 433080 AN: 833572 Hom.: 113654 Cov.: 32 AF XY: 0.519 AC XY: 199755 AN XY: 384994

African (AFR) AF: 0.176 AC: 2773 AN: 15784

American (AMR) AF: 0.621 AC: 611 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 2516 AN: 5152

East Asian (EAS) AF: 0.582 AC: 2111 AN: 3630

South Asian (SAS) AF: 0.476 AC: 7833 AN: 16460

European-Finnish (FIN) AF: 0.540 AC: 377 AN: 698

Middle Eastern (MID) AF: 0.518 AC: 840 AN: 1622

European-Non Finnish (NFE) AF: 0.528 AC: 402408 AN: 761936

Other (OTH) AF: 0.498 AC: 13611 AN: 27306

GnomAD4 genome AF: 0.445 AC: 67648 AN: 152070 Hom.: 16889 Cov.: 32 AF XY: 0.450 AC XY: 33458 AN XY: 74334

African (AFR) AF: 0.201 AC: 8344 AN: 41498

American (AMR) AF: 0.569 AC: 8693 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3466

East Asian (EAS) AF: 0.583 AC: 3015 AN: 5174

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4818

European-Finnish (FIN) AF: 0.573 AC: 6050 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36050 AN: 67962

Other (OTH) AF: 0.474 AC: 997 AN: 2104

Alfa AF: 0.486 Hom.: 31077

Bravo AF: 0.437

Asia WGS AF: 0.520 AC: 1806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.9
DANN	Benign	0.76
PhyloP100		0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3087519; hg19: chr16-11023208; COSMIC: COSV59329177; COSMIC: COSV59329177;