rs6498124

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.482-45G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,611,356 control chromosomes in the GnomAD database, including 245,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17844 hom., cov: 31)

Exomes 𝑓: 0.55 ( 227569 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.211

Publications

6 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:

ENSG00000308110 (HGNC:):

ENSG00000308110 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=-0.83).

BP6

Variant 16-10901993-G-T is Benign according to our data. Variant chr16-10901993-G-T is described in ClinVar as Benign. ClinVar VariationId is 1184676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 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.482-45G>T	intron	N/A	NP_000237.2
CIITA	NM_001286402.1		c.485-45G>T	intron	N/A	NP_001273331.1	A0A087X2I7
CIITA	NM_001379332.1		c.485-45G>T	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.482-45G>T	intron	N/A	ENSP00000316328.8
CIITA	ENST00000381835.9	TSL:1	c.481+435G>T	intron	N/A	ENSP00000371257.5	P33076-3
CIITA	ENST00000537380.1	TSL:1	n.482-45G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70886

AN:

151726

Hom.:

17843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.567

Gnomad OTH

AF:

0.465

GnomAD2 exomes

AF:

0.497

AC:

123574

AN:

248642

AF XY:

0.512

show subpopulations

Gnomad AFR exome

AF:

0.285

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.568

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.553

AC:

807245

AN:

1459512

Hom.:

227569

Cov.:

AF XY:

0.554

AC XY:

402406

AN XY:

726158

show subpopulations

African (AFR)

AF:

0.290

AC:

9690

AN:

33448

American (AMR)

AF:

0.330

AC:

14772

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.452

AC:

11811

AN:

26130

East Asian (EAS)

AF:

0.408

AC:

16192

AN:

39698

South Asian (SAS)

AF:

0.539

AC:

46470

AN:

86194

European-Finnish (FIN)

AF:

0.580

AC:

30384

AN:

52398

Middle Eastern (MID)

AF:

0.555

AC:

2869

AN:

5168

European-Non Finnish (NFE)

AF:

0.579

AC:

643738

AN:

1111486

Other (OTH)

AF:

0.520

AC:

31319

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

19471

38942

58412

77883

97354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17658

35316

52974

70632

88290

<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:

0.467

AC:

70904

AN:

151844

Hom.:

17844

Cov.:

AF XY:

0.465

AC XY:

34550

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.295

AC:

12207

AN:

41400

American (AMR)

AF:

0.388

AC:

5921

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1582

AN:

3464

East Asian (EAS)

AF:

0.429

AC:

2211

AN:

5150

South Asian (SAS)

AF:

0.523

AC:

2513

AN:

4806

European-Finnish (FIN)

AF:

0.586

AC:

6177

AN:

10538

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.567

AC:

38493

AN:

67912

Other (OTH)

AF:

0.463

AC:

974

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1777

3555

5332

7110

8887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.508

Hom.:

9282

Bravo

AF:

0.445

Asia WGS

AF:

0.388

AC:

1349

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

-0.83

CADD

Benign

1.7

(source)

DANN

Benign

0.72

PhyloP100

-0.21

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

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