Genetic Variant CIITA:c.2888+34C>T (chr16-10910293-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000246.4(CIITA):c.2888+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,589,638 control chromosomes in the GnomAD database, including 230,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18638 hom., cov: 32)

Exomes 𝑓: 0.54 ( 211812 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0120

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 16-10910293-C-T is Benign according to our data. Variant chr16-10910293-C-T is described in ClinVar as [Benign]. Clinvar id is 1184689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4 link	c.2888+34C>T		intron_variant	Intron 13 of 19	ENST00000324288.14	NP_000237.2	P33076A0A0B4J1S1Q66X48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 link	c.2888+34C>T		intron_variant	Intron 13 of 19	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74300

AN:

151944

Hom.:

18635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.459

Gnomad FIN

AF:

0.534

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.503

GnomAD3 exomes

AF:

0.485

AC:

117413

AN:

242124

Hom.:

29233

AF XY:

0.493

AC XY:

64564

AN XY:

130868

show subpopulations

Gnomad AFR exome

AF:

0.398

Gnomad AMR exome

AF:

0.322

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.372

Gnomad SAS exome

AF:

0.461

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.562

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.539

AC:

775146

AN:

1437576

Hom.:

211812

Cov.:

AF XY:

0.538

AC XY:

385397

AN XY:

715978

show subpopulations

Gnomad4 AFR exome

AF:

0.404

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.341

Gnomad4 SAS exome

AF:

0.465

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.567

Gnomad4 OTH exome

AF:

0.519

GnomAD4 genome

AF:

0.489

AC:

74335

AN:

152062

Hom.:

18638

Cov.:

AF XY:

0.485

AC XY:

36055

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.426

Gnomad4 ASJ

AF:

0.527

Gnomad4 EAS

AF:

0.370

Gnomad4 SAS

AF:

0.460

Gnomad4 FIN

AF:

0.534

Gnomad4 NFE

AF:

0.560

Gnomad4 OTH

AF:

0.503

Alfa

AF:

0.534

Hom.:

12926

Bravo

AF:

0.473

Asia WGS

AF:

0.425

AC:

1477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

MHC class II deficiency

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.4

DANN

Benign

0.78

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over