chr19-49661133-T-C

Position:

• chr19-49661133-T-C

Variant summary

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

The NM_001571.6(IRF3):​c.983-305A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 388,822 control chromosomes in the GnomAD database, including 44,414 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 0.52 (23755 hom., cov: 33)
  • Exomes 𝑓: 0.40 (20659 hom.)
• Consequence: IRF3 NM_001571.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRF3	NM_001571.6	c.983-305A>G		intron_variant		ENST00000377139.8	NP_001562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRF3	ENST00000377139.8	c.983-305A>G		intron_variant		1	NM_001571.6	ENSP00000366344	P1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78702 AN: 151988 Hom.: 23696 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.401 AC: 94878 AN: 236716 Hom.: 20659 AF XY: 0.405 AC XY: 49798 AN XY: 122942

Gnomad4 AFR exome AF: 0.840

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.366

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.518 AC: 78815 AN: 152106 Hom.: 23755 Cov.: 33 AF XY: 0.512 AC XY: 38056 AN XY: 74364

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.483

Alfa AF: 0.411 Hom.: 13382

Bravo AF: 0.544

Asia WGS AF: 0.539 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.63

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: rs10415576; hg19: chr19-50164390;