16-85902657-C-T

Variant names:

• chr16-85902657-C-T
• rs12924316
• NM_002163.4:c.-1-358C>T

Variant summary

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

The NM_002163.4(IRF8):​c.-1-358C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 330,642 control chromosomes in the GnomAD database, including 4,579 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 0.14 (1883 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2696 hom.)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.-1-358C>T		intron_variant	Intron 1 of 8	ENST00000268638.10	NP_002154.1
IRF8	XM_047434052.1	c.-204C>T		5_prime_UTR_variant	Exon 2 of 10		XP_047290008.1
IRF8	NM_001363907.1	c.-204C>T		upstream_gene_variant			NP_001350836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.-1-358C>T		intron_variant	Intron 1 of 8	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21736 AN: 152142 Hom.: 1883 Cov.: 32

Gnomad AFR AF: 0.0442

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.164 AC: 29217 AN: 178382 Hom.: 2696 Cov.: 0 AF XY: 0.159 AC XY: 15189 AN XY: 95520

Gnomad4 AFR exome AF: 0.0445

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.143 AC: 21731 AN: 152260 Hom.: 1883 Cov.: 32 AF XY: 0.143 AC XY: 10627 AN XY: 74448

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.168

Alfa AF: 0.0867 Hom.: 139

Bravo AF: 0.142

Asia WGS AF: 0.198 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.46

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: rs12924316; hg19: chr16-85936263;