chr16-85922438-A-T

Position:

• chr16-85922438-A-T

Variant summary

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

The NM_002163.4(IRF8):​c.*1156A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,200 control chromosomes in the GnomAD database, including 27,686 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 0.59 (27669 hom., cov: 32)
  • Exomes 𝑓: 0.50 (17 hom.)
• Consequence: IRF8 NM_002163.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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 (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRF8	NM_002163.4	c.*1156A>T		3_prime_UTR_variant	9/9	ENST00000268638.10
IRF8	NM_001363907.1	c.*1156A>T		3_prime_UTR_variant	9/9
IRF8	NM_001363908.1	c.*1156A>T		3_prime_UTR_variant	7/7
IRF8	XM_047434052.1	c.*1156A>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRF8	ENST00000268638.10	c.*1156A>T		3_prime_UTR_variant	9/9	1	NM_002163.4	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90124 AN: 151944 Hom.: 27616 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.597

GnomAD4 exome AF: 0.500 AC: 69 AN: 138 Hom.: 17 Cov.: 0 AF XY: 0.513 AC XY: 40 AN XY: 78

Gnomad4 EAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.593 AC: 90237 AN: 152062 Hom.: 27669 Cov.: 32 AF XY: 0.596 AC XY: 44333 AN XY: 74340

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.601

Alfa AF: 0.418 Hom.: 1278

Bravo AF: 0.613

Asia WGS AF: 0.711 AC: 2471 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	0.18
DANN	Benign	0.41

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: rs6638; hg19: chr16-85956044;