19-49662099-GGC-AGT

Variant names:

• chr19-49662099-GGC-AGT
• NM_001571.6:c.829_831delGCCinsACT
• IRF3 p.Ala277Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001571.6(IRF3):​c.829_831delGCCinsACT​(p.Ala277Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IRF3 NM_001571.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• Publications: 0 publications found

Genes affected

IRF3 (HGNC:6118): (interferon regulatory factor 3) This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. The protein plays an important role in the innate immune response against DNA and RNA viruses. Mutations in this gene are associated with Encephalopathy, acute, infection-induced, herpes-specific, 7. [provided by RefSeq, Sep 2020]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001571.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF3	NM_001571.6	MANE Select	c.829_831delGCCinsACT	p.Ala277Thr	missense	N/A	NP_001562.1	Q14653-1
	IRF3	NM_001197122.2		c.829_831delGCCinsACT	p.Ala277Thr	missense	N/A	NP_001184051.1	Q14653-4
	IRF3	NM_001197123.2		c.724_726delGCCinsACT	p.Ala242Thr	missense	N/A	NP_001184052.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRF3	ENST00000377139.8	TSL:1 MANE Select	c.829_831delGCCinsACT	p.Ala277Thr	missense	N/A	ENSP00000366344.3	Q14653-1
	IRF3	ENST00000601291.5	TSL:1	c.829_831delGCCinsACT	p.Ala277Thr	missense	N/A	ENSP00000471896.1	Q14653-4
	IRF3	ENST00000309877.11	TSL:1	c.829_831delGCCinsACT	p.Ala277Thr	missense	N/A	ENSP00000310127.6	Q14653-1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-50165356;