Genetic Variant CIITA:c.*5496T>C (chr16-10929351-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.763

Variant links:

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 links:

DEXI (HGNC:13267): (Dexi homolog)

DEXI links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4 link	c.*5496T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000324288.14	NP_000237.2	P33076A0A0B4J1S1Q66X48
DEXI	NM_014015.4 link	c.*358A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000331808.5	NP_054734.2	O95424

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 link	c.*5496T>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1
DEXI	ENST00000331808 link	c.*358A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_014015.4	ENSP00000330509.4		O95424

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67643

AN:

151952

Hom.:

16894

Cov.:

show subpopulations

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.:

AF XY:

0.519

AC XY:

199755

AN XY:

384994

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.582

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.540

Gnomad4 NFE exome

AF:

0.528

Gnomad4 OTH exome

AF:

0.498

GnomAD4 genome

AF:

0.445

AC:

67648

AN:

152070

Hom.:

16889

Cov.:

AF XY:

0.450

AC XY:

33458

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.201

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.467

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.530

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.401

Hom.:

2592

Bravo

AF:

0.437

Asia WGS

AF:

0.520

AC:

1806

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.9

DANN

Benign

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over