16-10902720-C-T

Position:

chr16-10902720-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000324288.14(CIITA):c.691C>T(p.Pro231Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000513 in 1,614,184 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P231P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 12 hom. )

Consequence

CIITA
ENST00000324288.14 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: 0.917

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006098479).

BP6

Variant 16-10902720-C-T is Benign according to our data. Variant chr16-10902720-C-T is described in ClinVar as [Benign]. Clinvar id is 528792.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-10902720-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000906 (138/152300) while in subpopulation EAS AF= 0.0207 (107/5176). AF 95% confidence interval is 0.0175. There are 0 homozygotes in gnomad4. There are 63 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	NM_000246.4 linkuse as main transcript	c.691C>T	p.Pro231Ser	missense_variant	8/20	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.691C>T	p.Pro231Ser	missense_variant	8/20	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.000913

AC:

139

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0208

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00189

AC:

475

AN:

251496

Hom.:

AF XY:

0.00170

AC XY:

231

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0250

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000472

AC:

690

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

309

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152300

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0207

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000668

Hom.:

Bravo

AF:

0.000805

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00152

AC:

184

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.9

DANN

Uncertain

0.99

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.69

T;T;T;T

MetaRNN

Benign

0.0061

T;T;T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

.;.;N;N

REVEL

Benign

0.090

Sift

Benign

0.15

.;.;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Vest4

0.13

MVP

0.79

MPC

0.13

ClinPred

0.039

GERP RS

1.2

gMVP

0.28

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