rs4781024

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000246.4(CIITA):c.3318-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,607,398 control chromosomes in the GnomAD database, including 122,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9427 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112952 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.591

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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

CIITA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-10923201-G-A is Benign according to our data. Variant chr16-10923201-G-A is described in ClinVar as Benign. ClinVar VariationId is 1184692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIITA	NM_000246.4	MANE Select	c.3318-27G>A	intron	N/A	NP_000237.2
CIITA	NM_001286402.1		c.3321-27G>A	intron	N/A	NP_001273331.1	A0A087X2I7
CIITA	NM_001379332.1		c.3321-27G>A	intron	N/A	NP_001366261.1	A0A087X2I7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CIITA	ENST00000324288.14	TSL:1 MANE Select	c.3318-27G>A	intron	N/A	ENSP00000316328.8
CIITA	ENST00000381835.9	TSL:1	c.1566-27G>A	intron	N/A	ENSP00000371257.5	P33076-3
CIITA	ENST00000886127.1		c.3420-27G>A	intron	N/A	ENSP00000556186.1

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51807

AN:

151932

Hom.:

9427

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.454

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.573

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.361

GnomAD2 exomes

AF:

0.367

AC:

91103

AN:

248480

AF XY:

0.378

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.245

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.404

Gnomad OTH exome

AF:

0.384

GnomAD4 exome

AF:

0.390

AC:

566944

AN:

1455346

Hom.:

112952

Cov.:

AF XY:

0.392

AC XY:

283706

AN XY:

724262

show subpopulations

African (AFR)

AF:

0.206

AC:

6869

AN:

33394

American (AMR)

AF:

0.250

AC:

11160

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

15066

AN:

26112

East Asian (EAS)

AF:

0.318

AC:

12623

AN:

39692

South Asian (SAS)

AF:

0.405

AC:

34905

AN:

86182

European-Finnish (FIN)

AF:

0.377

AC:

19041

AN:

50530

Middle Eastern (MID)

AF:

0.454

AC:

2616

AN:

5764

European-Non Finnish (NFE)

AF:

0.398

AC:

441529

AN:

1108716

Other (OTH)

AF:

0.384

AC:

23135

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

17669

35338

53007

70676

88345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13582

27164

40746

54328

67910

<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:

0.341

AC:

51814

AN:

152052

Hom.:

9427

Cov.:

AF XY:

0.339

AC XY:

25165

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.213

AC:

8846

AN:

41456

American (AMR)

AF:

0.302

AC:

4618

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

1982

AN:

3462

East Asian (EAS)

AF:

0.315

AC:

1625

AN:

5160

South Asian (SAS)

AF:

0.400

AC:

1928

AN:

4822

European-Finnish (FIN)

AF:

0.380

AC:

4019

AN:

10584

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.405

AC:

27489

AN:

67956

Other (OTH)

AF:

0.358

AC:

757

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1743

3486

5230

6973

8716

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.389

Hom.:

11457

Bravo

AF:

0.325

Asia WGS

AF:

0.295

AC:

1028

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class II deficiency (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.0

(source)

DANN

Benign

0.64

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over