rs7196089

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CIITA	NM_000246.4	c.2816+57G>A		intron_variant		ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14	c.2816+57G>A		intron_variant		1	NM_000246.4	ENSP00000316328	P4

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

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.294

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

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.273

Alfa AF: 0.237 Hom.: 1072

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

MHC class II deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

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	-0.82
CADD	Benign	2.6
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs7196089; hg19: chr16-11003101;