16-85899201-AGACGGCGGCAG-A

Variant names:

• chr16-85899201-AGACGGCGGCAG-A
• rs548041435
• NM_002163.4:c.-11_-2+1delACGGCGGCAGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002163.4(IRF8):​c.-11_-2+1delACGGCGGCAGG variant causes a splice donor, 5 prime UTR, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000723 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRF8 NM_002163.4 splice_donor, 5_prime_UTR, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.-11_-2+1delACGGCGGCAGG		splice_region_variant	Exon 1 of 9	ENST00000268638.10	NP_002154.1
IRF8	NM_002163.4	c.-11_-2+1delACGGCGGCAGG		splice_donor_variant, 5_prime_UTR_variant, intron_variant	Exon 1 of 9	ENST00000268638.10	NP_002154.1
IRF8	NM_002163.4	c.-11_-2+1delACGGCGGCAGG		non_coding_transcript_variant		ENST00000268638.10	NP_002154.1
IRF8	XM_047434052.1	c.-2677_-2667delACGGCGGCAGG		5_prime_UTR_variant	Exon 1 of 10		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638	c.-46_-36delGACGGCGGCAG		5_prime_UTR_variant	Exon 1 of 9	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74336

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Immunodeficiency 32B Uncertain:1

-

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

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: rs548041435; hg19: chr16-85932807;