Genetic Variant CIITA:c.*6393C>T (chr16-10930248-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000246.4(CIITA):c.*6393C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,152 control chromosomes in the GnomAD database, including 14,917 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 14910 hom., cov: 32)

Exomes 𝑓: 0.46 ( 7 hom. )

Consequence

CIITA
NM_000246.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.508

Publications

12 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 links:

DEXI (HGNC:13267): (Dexi homolog)

DEXI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4 link	c.*6393C>T		3_prime_UTR_variant	Exon 20 of 20	ENST00000324288.14	NP_000237.2
DEXI	NM_014015.4 link	c.*150-689G>A		intron_variant	Intron 1 of 1	ENST00000331808.5	NP_054734.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 link	c.*6393C>T		3_prime_UTR_variant	Exon 20 of 20	1	NM_000246.4	ENSP00000316328.8
DEXI	ENST00000331808.5 link	c.*150-689G>A		intron_variant	Intron 1 of 1	1	NM_014015.4	ENSP00000330509.4

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

63102

AN:

151958

Hom.:

14915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.470

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.403

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.558

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.444

GnomAD4 exome

AF:

0.459

AC:

AN:

Hom.:

Cov.:

AF XY:

0.423

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.611

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.400

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.415

AC:

63107

AN:

152078

Hom.:

14910

Cov.:

AF XY:

0.421

AC XY:

31272

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.176

AC:

7311

AN:

41498

American (AMR)

AF:

0.550

AC:

8408

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

1397

AN:

3470

East Asian (EAS)

AF:

0.575

AC:

2970

AN:

5168

South Asian (SAS)

AF:

0.429

AC:

2072

AN:

4826

European-Finnish (FIN)

AF:

0.558

AC:

5884

AN:

10552

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33583

AN:

67958

Other (OTH)

AF:

0.442

AC:

936

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1747

3495

5242

6990

8737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.473

Hom.:

34114

Bravo

AF:

0.407

Asia WGS

AF:

0.502

AC:

1744

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.73

(source)

DANN

Benign

0.66

PhyloP100

-0.51

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

Computational scores

Splicing

Publications

Other links and lift over