16-10895659-T-C

Position:

chr16-10895659-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000246.4(CIITA):c.200-10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,614,120 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0098 ( 99 hom. )

Consequence

CIITA
NM_000246.4 intron

Scores

Splicing: ADA: 0.0006234

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 16-10895659-T-C is Benign according to our data. Variant chr16-10895659-T-C is described in ClinVar as [Benign]. Clinvar id is 317676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-10895659-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00611 (931/152272) while in subpopulation SAS AF= 0.0139 (67/4826). AF 95% confidence interval is 0.0112. There are 3 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIITA	NM_000246.4 link	c.200-10T>C		intron_variant		ENST00000324288.14	NP_000237.2	P33076A0A0B4J1S1Q66X48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14 link	c.200-10T>C		intron_variant		1	NM_000246.4	ENSP00000316328.8		A0A0B4J1S1

Frequencies

GnomAD3 genomes

AF:

0.00609

AC:

926

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00387

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00922

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00897

AC:

2255

AN:

251456

Hom.:

AF XY:

0.00938

AC XY:

1275

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00926

Gnomad OTH exome

AF:

0.00635

GnomAD4 exome

AF:

0.00976

AC:

14270

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7379

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00616

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0203

Gnomad4 FIN exome

AF:

0.00374

Gnomad4 NFE exome

AF:

0.00997

Gnomad4 OTH exome

AF:

0.00873

GnomAD4 genome

AF:

0.00611

AC:

931

AN:

152272

Hom.:

Cov.:

AF XY:

0.00637

AC XY:

474

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00387

Gnomad4 NFE

AF:

0.00922

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00857

Hom.:

Bravo

AF:

0.00601

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

MHC class II deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00062

dbscSNV1_RF

Benign

0.050

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over