chr16-10922188-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000246.4(CIITA):c.3171C>T(p.Cys1057Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,726 control chromosomes in the GnomAD database, including 9,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 737 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9028 hom. )

Consequence

CIITA
NM_000246.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.73

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

MHC class II deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

CIITA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 16-10922188-C-T is Benign according to our data. Variant chr16-10922188-C-T is described in ClinVar as Benign. ClinVar VariationId is 317725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4 link	c.3171C>T	p.Cys1057Cys	synonymous_variant	Exon 17 of 20	ENST00000324288.14	NP_000237.2	P33076A0A0B4J1S1Q66X48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 link	c.3171C>T	p.Cys1057Cys	synonymous_variant	Exon 17 of 20	1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.0975

AC:

14834

AN:

152178

Hom.:

738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0738

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0968

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.0772

Gnomad FIN

AF:

0.0943

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.118

GnomAD2 exomes

AF:

0.103

AC:

25921

AN:

251430

AF XY:

0.103

show subpopulations

Gnomad AFR exome

AF:

0.0748

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0994

Gnomad EAS exome

AF:

0.165

Gnomad FIN exome

AF:

0.0962

Gnomad NFE exome

AF:

0.104

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.108

AC:

158382

AN:

1461430

Hom.:

9028

Cov.:

AF XY:

0.108

AC XY:

78600

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.0686

AC:

2296

AN:

33474

American (AMR)

AF:

0.105

AC:

4702

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0965

AC:

2523

AN:

26136

East Asian (EAS)

AF:

0.156

AC:

6201

AN:

39698

South Asian (SAS)

AF:

0.0866

AC:

7470

AN:

86238

European-Finnish (FIN)

AF:

0.0958

AC:

5116

AN:

53414

Middle Eastern (MID)

AF:

0.107

AC:

620

AN:

5768

European-Non Finnish (NFE)

AF:

0.110

AC:

122490

AN:

1111602

Other (OTH)

AF:

0.115

AC:

6964

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

7500

15001

22501

30002

37502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4574

9148

13722

18296

22870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0974

AC:

14833

AN:

152296

Hom.:

737

Cov.:

AF XY:

0.0973

AC XY:

7249

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0737

AC:

3062

AN:

41570

American (AMR)

AF:

0.121

AC:

1848

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0968

AC:

336

AN:

3470

East Asian (EAS)

AF:

0.168

AC:

868

AN:

5166

South Asian (SAS)

AF:

0.0767

AC:

370

AN:

4826

European-Finnish (FIN)

AF:

0.0943

AC:

1000

AN:

10610

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6919

AN:

68036

Other (OTH)

AF:

0.117

AC:

248

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

681

1363

2044

2726

3407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.103

Hom.:

2991

Bravo

AF:

0.102

Asia WGS

AF:

0.105

AC:

364

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.110

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:4

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Nov 21, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.79

(source)

DANN

Benign

0.85

PhyloP100

-1.7

PromoterAI

0.44

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over