16-85902786-T-TGGCTGCAGGC

Variant names:

• chr16-85902786-T-TGGCTGCAGGC
• ENST00000563180.1:c.-221_-220insCGGCTGCAGG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000563180.1(IRF8):​c.-221_-220insCGGCTGCAGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: IRF8 ENST00000563180.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.19

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-85902786-T-TGGCTGCAGGC is Benign according to our data. Variant chr16-85902786-T-TGGCTGCAGGC is described in ClinVar as [Benign]. Clinvar id is 2688429.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.-1-220_-1-219insCGGCTGCAGG		intron_variant	Intron 1 of 8	ENST00000268638.10	NP_002154.1
IRF8	XM_047434052.1	c.-66_-65insCGGCTGCAGG		5_prime_UTR_variant	Exon 2 of 10		XP_047290008.1
IRF8	NM_001363907.1	c.-75_-74insGGCTGCAGGC		upstream_gene_variant			NP_001350836.1
IRF8	NM_001363908.1	c.-736_-735insGGCTGCAGGC		upstream_gene_variant			NP_001350837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.-1-220_-1-219insCGGCTGCAGG		intron_variant	Intron 1 of 8	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 3

GnomAD4 genome Cov.: 34

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-85936392;