16-10907913-G-T

Position:

chr16-10907913-G-T

Variant summary

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

The NM_000246.4(CIITA):c.2421G>T(p.Leu807=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,577,540 control chromosomes in the GnomAD database, including 37,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3672 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33595 hom. )

Consequence

CIITA
NM_000246.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.737

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 16-10907913-G-T is Benign according to our data. Variant chr16-10907913-G-T is described in ClinVar as [Benign]. Clinvar id is 317712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.737 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 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.2421G>T	p.Leu807=	synonymous_variant	11/20	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.2421G>T	p.Leu807=	synonymous_variant	11/20	1	NM_000246.4	ENSP00000316328	P4

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32380

AN:

152106

Hom.:

3659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.189

GnomAD3 exomes

AF:

0.235

AC:

50851

AN:

216436

Hom.:

7015

AF XY:

0.225

AC XY:

26301

AN XY:

116916

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.445

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.145

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.211

AC:

300723

AN:

1425316

Hom.:

33595

Cov.:

AF XY:

0.209

AC XY:

147769

AN XY:

705370

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.204

Gnomad4 SAS exome

AF:

0.203

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.213

AC:

32425

AN:

152224

Hom.:

3672

Cov.:

AF XY:

0.213

AC XY:

15876

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.220

Gnomad4 EAS

AF:

0.154

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.217

Hom.:

1019

Bravo

AF:

0.225

Asia WGS

AF:

0.235

AC:

817

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

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

-0.64

CADD

Benign

9.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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