rs4780334

Variant names:

• chr16-10908769-G-A
• rs4780334
• NM_000246.4:c.2658-260G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-10908769-G-A
• chr16-10908769-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.2658-260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 605,790 control chromosomes in the GnomAD database, including 146,525 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 0.66 (33337 hom., cov: 32)
  • Exomes 𝑓: 0.70 (113188 hom.)
• Consequence: CIITA NM_000246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000308110 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	NM_000246.4	MANE Select	c.2658-260G>A		intron	N/A	NP_000237.2
	CIITA	NM_001286402.1		c.2661-260G>A		intron	N/A	NP_001273331.1	A0A087X2I7
	CIITA	NM_001379332.1		c.2661-260G>A		intron	N/A	NP_001366261.1	A0A087X2I7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000324288.14	TSL:1 MANE Select	c.2658-260G>A		intron	N/A	ENSP00000316328.8
	CIITA	ENST00000381835.9	TSL:1	c.860-214G>A		intron	N/A	ENSP00000371257.5	P33076-3
	CIITA	ENST00000573309.5	TSL:1	n.3248G>A		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99591 AN: 151886 Hom.: 33335 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.681

GnomAD4 exome AF: 0.703 AC: 318891 AN: 453786 Hom.: 113188 Cov.: 4 AF XY: 0.706 AC XY: 169344 AN XY: 239752

African (AFR) AF: 0.527 AC: 6669 AN: 12660

American (AMR) AF: 0.542 AC: 10887 AN: 20090

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 9938 AN: 13928

East Asian (EAS) AF: 0.784 AC: 24234 AN: 30926

South Asian (SAS) AF: 0.732 AC: 33752 AN: 46088

European-Finnish (FIN) AF: 0.755 AC: 22056 AN: 29228

Middle Eastern (MID) AF: 0.685 AC: 1363 AN: 1990

European-Non Finnish (NFE) AF: 0.705 AC: 192117 AN: 272696

Other (OTH) AF: 0.683 AC: 17875 AN: 26180

GnomAD4 genome AF: 0.655 AC: 99627 AN: 152004 Hom.: 33337 Cov.: 32 AF XY: 0.658 AC XY: 48863 AN XY: 74304

African (AFR) AF: 0.526 AC: 21796 AN: 41418

American (AMR) AF: 0.602 AC: 9195 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3472

East Asian (EAS) AF: 0.841 AC: 4354 AN: 5176

South Asian (SAS) AF: 0.743 AC: 3587 AN: 4826

European-Finnish (FIN) AF: 0.771 AC: 8146 AN: 10568

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47785 AN: 67958

Other (OTH) AF: 0.678 AC: 1435 AN: 2116

Alfa AF: 0.683 Hom.: 145958

Bravo AF: 0.634

Asia WGS AF: 0.720 AC: 2504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.51
PhyloP100		-0.055
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: rs4780334; hg19: chr16-11002626;