rs7196089

Variant names:

• chr16-10909244-G-A
• rs7196089
• NM_000246.4:c.2816+57G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10909244-G-A
• chr16-10909244-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000246.4(CIITA):​c.2816+57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,580,364 control chromosomes in the GnomAD database, including 68,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6104 hom., cov: 33)
  • Exomes 𝑓: 0.29 (62185 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.200
• Publications: 10 publications found

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)

ENSG00000308110 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-10909244-G-A is Benign according to our data. Variant chr16-10909244-G-A is described in ClinVar as Benign. ClinVar VariationId is 1184688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4	c.2816+57G>A		intron_variant	Intron 12 of 19	ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14	c.2816+57G>A		intron_variant	Intron 12 of 19	1	NM_000246.4	ENSP00000316328.8

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42283 AN: 152076 Hom.: 6093 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.270

GnomAD4 exome AF: 0.291 AC: 415600 AN: 1428170 Hom.: 62185 AF XY: 0.290 AC XY: 206312 AN XY: 712314

African (AFR) AF: 0.246 AC: 8058 AN: 32810

American (AMR) AF: 0.473 AC: 20986 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7568 AN: 25928

East Asian (EAS) AF: 0.206 AC: 8145 AN: 39514

South Asian (SAS) AF: 0.262 AC: 22329 AN: 85120

European-Finnish (FIN) AF: 0.243 AC: 12834 AN: 52864

Middle Eastern (MID) AF: 0.281 AC: 1595 AN: 5668

European-Non Finnish (NFE) AF: 0.292 AC: 316634 AN: 1082612

Other (OTH) AF: 0.294 AC: 17451 AN: 59306

GnomAD4 genome AF: 0.278 AC: 42335 AN: 152194 Hom.: 6104 Cov.: 33 AF XY: 0.278 AC XY: 20711 AN XY: 74406

African (AFR) AF: 0.245 AC: 10158 AN: 41532

American (AMR) AF: 0.374 AC: 5726 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 976 AN: 3466

East Asian (EAS) AF: 0.157 AC: 812 AN: 5164

South Asian (SAS) AF: 0.251 AC: 1209 AN: 4822

European-Finnish (FIN) AF: 0.230 AC: 2435 AN: 10600

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20079 AN: 68000

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.238 Hom.: 1100

Bravo AF: 0.289

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

MHC class II deficiency Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7196089; hg19: chr16-11003101; COSMIC: COSV107405123; COSMIC: COSV107405123;