chr16-85911217-T-G

Position:

• chr16-85911217-T-G

Variant summary

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

The NM_002163.4(IRF8):​c.359-353T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,148 control chromosomes in the GnomAD database, including 13,741 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 (13741 hom., cov: 34)
• Consequence: IRF8 NM_002163.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF8	NM_002163.4	c.359-353T>G		intron_variant		ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1	c.389-353T>G		intron_variant			NP_001350836.1
IRF8	NM_001363908.1	c.-148-353T>G		intron_variant			NP_001350837.1
IRF8	XM_047434052.1	c.389-353T>G		intron_variant			XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.359-353T>G		intron_variant		1	NM_002163.4	ENSP00000268638	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62322 AN: 152030 Hom.: 13689 Cov.: 34

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.414

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62428 AN: 152148 Hom.: 13741 Cov.: 34 AF XY: 0.409 AC XY: 30451 AN XY: 74384

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.420

Alfa AF: 0.344 Hom.: 15226

Bravo AF: 0.418

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.62

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: rs2292982; hg19: chr16-85944823;