rs305077

chr16-85909860-T-Cchr16-85909860-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000563180.1(IRF8):c.*664T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,462 control chromosomes in the GnomAD database, including 13,795 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 (13787 hom., cov: 33)
  • Exomes 𝑓: 0.23 (8 hom.)
• Consequence: IRF8 ENST00000563180.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF8	NM_002163.4	c.358+687T>C		intron_variant		ENST00000268638.10
IRF8	NM_001363907.1	c.388+687T>C		intron_variant
IRF8	NM_001363908.1	c.-149+687T>C		intron_variant
IRF8	XM_047434052.1	c.388+687T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF8	ENST00000268638.10	c.358+687T>C		intron_variant		1	NM_002163.4	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62074 AN: 152006 Hom.: 13745 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.228 AC: 77 AN: 338 Hom.: 8 Cov.: 0 AF XY: 0.208 AC XY: 35 AN XY: 168

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.0769

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.409 AC: 62167 AN: 152124 Hom.: 13787 Cov.: 33 AF XY: 0.407 AC XY: 30261 AN XY: 74384

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.411

Alfa AF: 0.313 Hom.: 1367

Bravo AF: 0.413

Asia WGS AF: 0.342 AC: 1185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.21
Dann	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs305077; hg19: chr16-85943466;