rs2304207

Positions:

• chr19-49664469-C-G
• chr19-49664469-C-T

Variant summary

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

The NM_001197123.2(IRF3):​c.34G>C​(p.Val12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,530,516 control chromosomes in the GnomAD database, including 19,015 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict 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 (1609 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17406 hom.)
• Consequence: IRF3 NM_001197123.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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]

IRF3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF3	NM_001571.6	c.165+205G>C		intron_variant		ENST00000377139.8	NP_001562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF3	ENST00000377139.8	c.165+205G>C		intron_variant		1	NM_001571.6	ENSP00000366344.3

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21032 AN: 151926 Hom.: 1608 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.139 AC: 20200 AN: 144962 Hom.: 1676 AF XY: 0.147 AC XY: 11660 AN XY: 79418

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.0755

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0225

Gnomad SAS exome AF: 0.201

Gnomad FIN exome AF: 0.163

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.150

GnomAD4 exome AF: 0.154 AC: 212044 AN: 1378472 Hom.: 17406 Cov.: 31 AF XY: 0.156 AC XY: 106510 AN XY: 681046

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0196

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.138 AC: 21041 AN: 152044 Hom.: 1609 Cov.: 32 AF XY: 0.137 AC XY: 10174 AN XY: 74280

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.128

Alfa AF: 0.139 Hom.: 1014

Bravo AF: 0.130

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs2304207; hg19: chr19-50167726; COSMIC: COSV55862786; COSMIC: COSV55862786;