16-10907837-T-C

Position:

chr16-10907837-T-C

Variant summary

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

The NM_000246.4(CIITA):c.2345T>C(p.Val782Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,613,464 control chromosomes in the GnomAD database, including 5,099 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.062 ( 366 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4733 hom. )

Consequence

CIITA
NM_000246.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.09

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 (MetaRNN=0.0027588606).

BP6

Variant 16-10907837-T-C is Benign according to our data. Variant chr16-10907837-T-C is described in ClinVar as [Benign]. Clinvar id is 317709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0809 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.2345T>C	p.Val782Ala	missense_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.2345T>C	p.Val782Ala	missense_variant	11/20	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.0622

AC:

9464

AN:

152094

Hom.:

366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0556

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0730

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.0808

GnomAD3 exomes

AF:

0.0629

AC:

15563

AN:

247422

Hom.:

605

AF XY:

0.0650

AC XY:

8749

AN XY:

134604

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.0376

Gnomad ASJ exome

AF:

0.0638

Gnomad EAS exome

AF:

0.000607

Gnomad SAS exome

AF:

0.0528

Gnomad FIN exome

AF:

0.0722

Gnomad NFE exome

AF:

0.0851

Gnomad OTH exome

AF:

0.0721

GnomAD4 exome

AF:

0.0773

AC:

112944

AN:

1461252

Hom.:

4733

Cov.:

AF XY:

0.0775

AC XY:

56362

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.0401

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.0544

Gnomad4 FIN exome

AF:

0.0730

Gnomad4 NFE exome

AF:

0.0851

Gnomad4 OTH exome

AF:

0.0764

GnomAD4 genome

AF:

0.0623

AC:

9476

AN:

152212

Hom.:

366

Cov.:

AF XY:

0.0618

AC XY:

4603

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0354

Gnomad4 AMR

AF:

0.0555

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.0478

Gnomad4 FIN

AF:

0.0730

Gnomad4 NFE

AF:

0.0827

Gnomad4 OTH

AF:

0.0799

Alfa

AF:

0.0794

Hom.:

771

Bravo

AF:

0.0609

TwinsUK

AF:

0.0809

AC:

300

ALSPAC

AF:

0.0848

AC:

327

ESP6500AA

AF:

0.0364

AC:

159

ESP6500EA

AF:

0.0835

AC:

717

ExAC

AF:

0.0629

AC:

7630

EpiCase

AF:

0.0865

EpiControl

AF:

0.0891

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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	- -
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	- -

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 -

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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0050

DANN

Benign

0.46

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.97

.;N

REVEL

Benign

0.20

Sift

Benign

0.59

.;T

Sift4G

Benign

1.0

T;T

Vest4

0.025

MPC

0.15

ClinPred

0.0035

GERP RS

-6.0

gMVP

0.16

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