Variant rs4781016 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.629-116C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,299,786 control chromosomes in the GnomAD database, including 52,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6092 hom., cov: 33)

Exomes 𝑓: 0.28 ( 46612 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

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=-0.8).

BP6

Variant 16-10902542-C-A is Benign according to our data. Variant chr16-10902542-C-A is described in ClinVar as [Benign]. Clinvar id is 1184677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.382 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.629-116C>A		intron_variant		ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 linkuse as main transcript	c.629-116C>A		intron_variant		1	NM_000246.4	ENSP00000316328	P4

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

42011

AN:

152034

Hom.:

6088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.278

AC:

319425

AN:

1147634

Hom.:

46612

AF XY:

0.276

AC XY:

160229

AN XY:

580694

show subpopulations

Gnomad4 AFR exome

AF:

0.241

Gnomad4 AMR exome

AF:

0.473

Gnomad4 ASJ exome

AF:

0.393

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.233

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.276

AC:

42049

AN:

152152

Hom.:

6092

Cov.:

AF XY:

0.275

AC XY:

20458

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.247

Gnomad4 AMR

AF:

0.390

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.158

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.288

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.296

Hom.:

9442

Bravo

AF:

0.289

Asia WGS

AF:

0.257

AC:

894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.54

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