16-10930248-C-T

Variant names:

• chr16-10930248-C-T
• rs4072865
• NM_000246.4:c.*6393C>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.*6393C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,152 control chromosomes in the GnomAD database, including 14,917 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 0.41 (14910 hom., cov: 32)
  • Exomes 𝑓: 0.46 (7 hom.)
• Consequence: CIITA NM_000246.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 12 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]

DEXI (HGNC:13267): (Dexi homolog)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 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.*6393C>T		3_prime_UTR	Exon 20 of 20	NP_000237.2
	DEXI	NM_014015.4	MANE Select	c.*150-689G>A		intron	N/A	NP_054734.2
	CIITA	NM_001286403.2		c.*6393C>T		3_prime_UTR	Exon 18 of 18	NP_001273332.1	P33076-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIITA	ENST00000324288.14	TSL:1 MANE Select	c.*6393C>T		3_prime_UTR	Exon 20 of 20	ENSP00000316328.8
	DEXI	ENST00000331808.5	TSL:1 MANE Select	c.*150-689G>A		intron	N/A	ENSP00000330509.4	O95424
	CIITA	ENST00000886125.1		c.*22+6923C>T		intron	N/A	ENSP00000556184.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63102 AN: 151958 Hom.: 14915 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.459 AC: 34 AN: 74 Hom.: 7 Cov.: 0 AF XY: 0.423 AC XY: 22 AN XY: 52

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.833 AC: 5 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.611 AC: 11 AN: 18

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.400 AC: 16 AN: 40

Other (OTH) AF: 0.250 AC: 2 AN: 8

GnomAD4 genome AF: 0.415 AC: 63107 AN: 152078 Hom.: 14910 Cov.: 32 AF XY: 0.421 AC XY: 31272 AN XY: 74316

African (AFR) AF: 0.176 AC: 7311 AN: 41498

American (AMR) AF: 0.550 AC: 8408 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3470

East Asian (EAS) AF: 0.575 AC: 2970 AN: 5168

South Asian (SAS) AF: 0.429 AC: 2072 AN: 4826

European-Finnish (FIN) AF: 0.558 AC: 5884 AN: 10552

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33583 AN: 67958

Other (OTH) AF: 0.442 AC: 936 AN: 2116

Alfa AF: 0.473 Hom.: 34114

Bravo AF: 0.407

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.73
DANN	Benign	0.66
PhyloP100		-0.51
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: rs4072865; hg19: chr16-11024105;