rs771773479

Variant names:

• chr16-85920201-C-A
• NM_002163.4:c.1081C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-85920201-C-A
• chr16-85920201-C-G
• chr16-85920201-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002163.4(IRF8):​c.1081C>A​(p.Arg361Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,420 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R361G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IRF8 NM_002163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF8	NM_002163.4	c.1081C>A	p.Arg361Ser	missense_variant	Exon 8 of 9	ENST00000268638.10	NP_002154.1
IRF8	NM_001363907.1	c.1111C>A	p.Arg371Ser	missense_variant	Exon 8 of 9		NP_001350836.1
IRF8	NM_001363908.1	c.469C>A	p.Arg157Ser	missense_variant	Exon 6 of 7		NP_001350837.1
IRF8	XM_047434052.1	c.1111C>A	p.Arg371Ser	missense_variant	Exon 9 of 10		XP_047290008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF8	ENST00000268638.10	c.1081C>A	p.Arg361Ser	missense_variant	Exon 8 of 9	1	NM_002163.4	ENSP00000268638.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400420 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 698896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.44e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	D;T;T
Eigen	Benign	0.093
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.42	T;T;T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.035	D;T;T
Polyphen		0.28	B;.;.
Vest4		0.56
MutPred		0.45		Gain of ubiquitination at K363 (P = 0.0747);.;.;
MVP		0.66
MPC		1.6
ClinPred		0.87	D
GERP RS		5.2
Varity_R		0.36
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-85953807; COSMIC: COSV99236947; COSMIC: COSV99236947;