chr16-10909070-A-G

Variant names:

Variant summary

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

The NM_001286402.1(CIITA):c.2702A>G(p.Gln901Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 1,614,164 control chromosomes in the GnomAD database, including 789,429 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q901K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.93 ( 67250 hom., cov: 33)

Exomes 𝑓: 0.99 ( 722179 hom. )

Consequence

CIITA
NM_001286402.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.922

Publications

34 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:

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 (MetaRNN=9.571822E-7).

BP6

Variant 16-10909070-A-G is Benign according to our data. Variant chr16-10909070-A-G is described in ClinVar as Benign. ClinVar VariationId is 317718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286402.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIITA	NM_000246.4	MANE Select	c.2699A>G	p.Gln900Arg	missense	Exon 12 of 20	NP_000237.2
CIITA	NM_001286402.1		c.2702A>G	p.Gln901Arg	missense	Exon 12 of 20	NP_001273331.1
CIITA	NM_001379332.1		c.2702A>G	p.Gln901Arg	missense	Exon 12 of 20	NP_001366261.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CIITA	ENST00000324288.14	TSL:1 MANE Select	c.2699A>G	p.Gln900Arg	missense	Exon 12 of 20	ENSP00000316328.8
CIITA	ENST00000381835.9	TSL:1	c.947A>G	p.Gln316Arg	missense	Exon 10 of 18	ENSP00000371257.5
CIITA	ENST00000537380.1	TSL:1	n.1007-1118A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.935

AC:

142214

AN:

152164

Hom.:

67214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.772

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.977

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.996

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.994

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.953

GnomAD2 exomes

AF:

0.983

AC:

246985

AN:

251276

AF XY:

0.988

show subpopulations

Gnomad AFR exome

AF:

0.766

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.992

GnomAD4 exome

AF:

0.993

AC:

1452103

AN:

1461882

Hom.:

722179

Cov.:

AF XY:

0.994

AC XY:

723049

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.764

AC:

25567

AN:

33478

American (AMR)

AF:

0.988

AC:

44185

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

26136

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39700

AN:

39700

South Asian (SAS)

AF:

0.998

AC:

86050

AN:

86258

European-Finnish (FIN)

AF:

1.00

AC:

53417

AN:

53418

Middle Eastern (MID)

AF:

0.993

AC:

5725

AN:

5768

European-Non Finnish (NFE)

AF:

1.00

AC:

1111819

AN:

1112004

Other (OTH)

AF:

0.985

AC:

59504

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

498

997

1495

1994

2492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21656

43312

64968

86624

108280

<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:

0.934

AC:

142303

AN:

152282

Hom.:

67250

Cov.:

AF XY:

0.937

AC XY:

69760

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.772

AC:

32057

AN:

41508

American (AMR)

AF:

0.977

AC:

14947

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

3472

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5188

AN:

5188

South Asian (SAS)

AF:

0.996

AC:

4808

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10627

AN:

10628

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67984

AN:

68040

Other (OTH)

AF:

0.953

AC:

2017

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

413

827

1240

1654

2067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.976

Hom.:

194515

Bravo

AF:

0.925

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

3853

ESP6500AA

AF:

0.764

AC:

3358

ESP6500EA

AF:

0.999

AC:

8595

ExAC

AF:

0.979

AC:

118810

Asia WGS

AF:

0.989

AC:

3440

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

MHC class II deficiency (4)

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.8

(source)

DANN

Benign

0.65

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.032

MetaRNN

Benign

9.6e-7

MetaSVM

Benign

-0.98

PhyloP100

0.92

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.2

REVEL

Benign

0.064

Sift

Benign

0.52

Sift4G

Benign

0.35

Vest4

0.024

MPC

0.13

ClinPred

0.0020

GERP RS

-0.25

gMVP

0.30

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over