16-10908057-G-A

Position:

chr16-10908057-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000246.4(CIITA):c.2565G>A(p.Ala855Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 1,612,930 control chromosomes in the GnomAD database, including 5,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 370 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4689 hom. )

Consequence

CIITA
NM_000246.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -5.02

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-10908057-G-A is Benign according to our data. Variant chr16-10908057-G-A is described in ClinVar as [Benign]. Clinvar id is 317714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0809 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.2565G>A	p.Ala855Ala	synonymous_variant	11/20	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.2565G>A	p.Ala855Ala	synonymous_variant	11/20	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.0621

AC:

9450

AN:

152208

Hom.:

370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0350

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0550

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.0729

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0826

Gnomad OTH

AF:

0.0803

GnomAD3 exomes

AF:

0.0635

AC:

15567

AN:

245318

Hom.:

628

AF XY:

0.0655

AC XY:

8740

AN XY:

133364

show subpopulations

Gnomad AFR exome

AF:

0.0355

Gnomad AMR exome

AF:

0.0375

Gnomad ASJ exome

AF:

0.0641

Gnomad EAS exome

AF:

0.000666

Gnomad SAS exome

AF:

0.0524

Gnomad FIN exome

AF:

0.0734

Gnomad NFE exome

AF:

0.0863

Gnomad OTH exome

AF:

0.0727

GnomAD4 exome

AF:

0.0770

AC:

112457

AN:

1460604

Hom.:

4689

Cov.:

AF XY:

0.0772

AC XY:

56102

AN XY:

726516

show subpopulations

Gnomad4 AFR exome

AF:

0.0361

Gnomad4 AMR exome

AF:

0.0397

Gnomad4 ASJ exome

AF:

0.0609

Gnomad4 EAS exome

AF:

0.000832

Gnomad4 SAS exome

AF:

0.0540

Gnomad4 FIN exome

AF:

0.0730

Gnomad4 NFE exome

AF:

0.0847

Gnomad4 OTH exome

AF:

0.0760

GnomAD4 genome

AF:

0.0621

AC:

9461

AN:

152326

Hom.:

370

Cov.:

AF XY:

0.0618

AC XY:

4600

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0352

Gnomad4 AMR

AF:

0.0549

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0474

Gnomad4 FIN

AF:

0.0729

Gnomad4 NFE

AF:

0.0827

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0727

Hom.:

210

Bravo

AF:

0.0607

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.082

DANN

Benign

0.50

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