rs7189406

Variant names:

• chr16-10899631-G-A
• rs7189406
• NM_000246.4:c.436+629G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10899631-G-A
• chr16-10899631-G-C
• chr16-10899631-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000246.4(CIITA):​c.436+629G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,104 control chromosomes in the GnomAD database, including 46,602 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 0.75 (46602 hom., cov: 32)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.37
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4	c.436+629G>A		intron_variant	Intron 5 of 19	ENST00000324288.14	NP_000237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIITA	ENST00000324288.14	c.436+629G>A		intron_variant	Intron 5 of 19	1	NM_000246.4	ENSP00000316328.8

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114641 AN: 151986 Hom.: 46600 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.754 AC: 114666 AN: 152104 Hom.: 46602 Cov.: 32 AF XY: 0.749 AC XY: 55689 AN XY: 74368

African (AFR) AF: 0.476 AC: 19697 AN: 41416

American (AMR) AF: 0.613 AC: 9370 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3146 AN: 3466

East Asian (EAS) AF: 0.542 AC: 2814 AN: 5190

South Asian (SAS) AF: 0.799 AC: 3848 AN: 4818

European-Finnish (FIN) AF: 0.934 AC: 9905 AN: 10600

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63109 AN: 68024

Other (OTH) AF: 0.786 AC: 1659 AN: 2112

Alfa AF: 0.851 Hom.: 150729

Bravo AF: 0.711

Asia WGS AF: 0.677 AC: 2354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.52
PhyloP100		-4.4
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: rs7189406; hg19: chr16-10993488;