ENST00000563180.1:c.-229_-220delGGCTGCAGGT

Variant names:

• chr16-85902783-TGGTGGCTGCA-T
• rs29001489
• ENST00000563180.1:c.-229_-220delGGCTGCAGGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000563180.1(IRF8):​c.-229_-220delGGCTGCAGGT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF8 ENST00000563180.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 0 publications found

Genes affected

IRF8 (HGNC:5358): (interferon regulatory factor 8) Interferon consensus sequence-binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Proteins of this family are composed of a conserved DNA-binding domain in the N-terminal region and a divergent C-terminal region that serves as the regulatory domain. The IRF family proteins bind to the IFN-stimulated response element (ISRE) and regulate expression of genes stimulated by type I IFNs, namely IFN-alpha and IFN-beta. IRF family proteins also control expression of IFN-alpha and IFN-beta-regulated genes that are induced by viral infection. [provided by RefSeq, Jul 2008]

IRF8 Gene-Disease associations (from GenCC):

• Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Illumina
• immunodeficiency 32B

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.-1-228_-1-219delGGCTGCAGGT		intron_variant	Intron 1 of 8	ENST00000268638.10	NP_002154.1
IRF8	XM_047434052.1	c.-74_-65delGGCTGCAGGT		5_prime_UTR_variant	Exon 2 of 10		XP_047290008.1
IRF8	NM_001363907.1	c.-77_-68delGGTGGCTGCA		upstream_gene_variant			NP_001350836.1
IRF8	NM_001363908.1	c.-738_-729delGGTGGCTGCA		upstream_gene_variant			NP_001350837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.-1-228_-1-219delGGCTGCAGGT		intron_variant	Intron 1 of 8	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 416516 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 221838

African (AFR) AF: 0.00 AC: 0 AN: 11838

American (AMR) AF: 0.00 AC: 0 AN: 21054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13128

East Asian (EAS) AF: 0.00 AC: 0 AN: 26626

South Asian (SAS) AF: 0.00 AC: 0 AN: 47090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1800

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 246916

Other (OTH) AF: 0.00 AC: 0 AN: 23748

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs29001489; hg19: chr16-85936389;