chr16-85902783-T-TGGTGGCTGCA

Position:

• chr16-85902783-T-TGGTGGCTGCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000563180.1(IRF8):​c.-229_-220dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (31791 hom., cov: 0)
  • Exomes 𝑓: 0.51 (58536 hom.)
• Consequence: IRF8 ENST00000563180.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.310

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 16-85902783-T-TGGTGGCTGCA is Benign according to our data. Variant chr16-85902783-T-TGGTGGCTGCA is described in ClinVar as [Benign]. Clinvar id is 2688522.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF8	NM_002163.4	c.-1-228_-1-219dup		intron_variant		ENST00000268638.10	NP_002154.1
IRF8	XM_047434052.1	c.-74_-65dup		5_prime_UTR_variant	2/10		XP_047290008.1
IRF8	NM_001363907.1			upstream_gene_variant			NP_001350836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.-1-228_-1-219dup		intron_variant		1	NM_002163.4	ENSP00000268638	P1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93338 AN: 151412 Hom.: 31717 Cov.: 0

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.511 AC: 212330 AN: 415618 Hom.: 58536 Cov.: 3 AF XY: 0.507 AC XY: 112274 AN XY: 221320

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.485

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.617 AC: 93474 AN: 151532 Hom.: 31791 Cov.: 0 AF XY: 0.621 AC XY: 45981 AN XY: 74054

Gnomad4 AFR AF: 0.896

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.602

Alfa AF: 0.312 Hom.: 451

Asia WGS AF: 0.725 AC: 2517 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 80. 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

LitVar

Other links and lift over

dbSNP: rs29001489; hg19: chr16-85936389;