rs6498122

Variant names:

• chr16-10900325-G-A
• rs6498122
• NM_000246.4:c.437-1189G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10900325-G-A
• chr16-10900325-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.437-1189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,170 control chromosomes in the GnomAD database, including 44,659 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 0.76 (44659 hom., cov: 33)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIITA	NM_000246.4	c.437-1189G>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.437-1189G>A		intron_variant	Intron 5 of 19	1	NM_000246.4	ENSP00000316328.8

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114870 AN: 152052 Hom.: 44646 Cov.: 33

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.755 AC: 114923 AN: 152170 Hom.: 44659 Cov.: 33 AF XY: 0.763 AC XY: 56778 AN XY: 74400

African (AFR) AF: 0.556 AC: 23043 AN: 41474

American (AMR) AF: 0.855 AC: 13079 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2909 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4319 AN: 5184

South Asian (SAS) AF: 0.814 AC: 3927 AN: 4822

European-Finnish (FIN) AF: 0.895 AC: 9497 AN: 10612

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55477 AN: 67998

Other (OTH) AF: 0.790 AC: 1666 AN: 2110

Alfa AF: 0.802 Hom.: 67066

Bravo AF: 0.744

Asia WGS AF: 0.782 AC: 2720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.26
PhyloP100		-0.54
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: rs6498122; hg19: chr16-10994182;