Variant 16-10901993-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000246.4(CIITA):c.482-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,611,356 control chromosomes in the GnomAD database, including 245,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17844 hom., cov: 31)

Exomes 𝑓: 0.55 ( 227569 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.211

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:

CIITA (HGNC:):

CIITA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-10901993-G-T is Benign according to our data. Variant chr16-10901993-G-T is described in ClinVar as [Benign]. Clinvar id is 1184676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	NM_000246.4 linkuse as main transcript	c.482-45G>T		intron_variant		ENST00000324288.14	NP_000237.2	P33076A0A0B4J1S1Q66X48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 linkuse as main transcript	c.482-45G>T		intron_variant		1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70886

AN:

151726

Hom.:

17843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.497

AC:

123574

AN:

248642

Hom.:

32477

AF XY:

0.512

AC XY:

68953

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.434

Gnomad SAS exome

AF:

0.531

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.553

AC:

807245

AN:

1459512

Hom.:

227569

Cov.:

AF XY:

0.554

AC XY:

402406

AN XY:

726158

show subpopulations

Gnomad4 AFR exome

AF:

0.290

Gnomad4 AMR exome

AF:

0.330

Gnomad4 ASJ exome

AF:

0.452

Gnomad4 EAS exome

AF:

0.408

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.580

Gnomad4 NFE exome

AF:

0.579

Gnomad4 OTH exome

AF:

0.520

GnomAD4 genome

AF:

0.467

AC:

70904

AN:

151844

Hom.:

17844

Cov.:

AF XY:

0.465

AC XY:

34550

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.586

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.514

Hom.:

7944

Bravo

AF:

0.445

Asia WGS

AF:

0.388

AC:

1349

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

MHC class II deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

0.72

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