rs10415576

Variant names:

• chr19-49661133-T-C
• rs10415576
• NM_001571.6:c.983-305A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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: Benign. The variant received -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.

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.983-305A>G		intron	N/A	NP_001562.1	Q14653-1
	IRF3	NM_001197122.2		c.983-289A>G		intron	N/A	NP_001184051.1	Q14653-4
	IRF3	NM_001197123.2		c.878-305A>G		intron	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.983-305A>G		intron	N/A	ENSP00000366344.3	Q14653-1
	IRF3	ENST00000601291.5	TSL:1	c.983-289A>G		intron	N/A	ENSP00000471896.1	Q14653-4
	IRF3	ENST00000309877.11	TSL:1	c.983-305A>G		intron	N/A	ENSP00000310127.6	Q14653-1

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

African (AFR) AF: 0.840 AC: 5193 AN: 6180

American (AMR) AF: 0.473 AC: 3476 AN: 7344

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 3116 AN: 8078

East Asian (EAS) AF: 0.366 AC: 5318 AN: 14526

South Asian (SAS) AF: 0.511 AC: 11309 AN: 22142

European-Finnish (FIN) AF: 0.306 AC: 4656 AN: 15198

Middle Eastern (MID) AF: 0.502 AC: 587 AN: 1170

European-Non Finnish (NFE) AF: 0.373 AC: 54935 AN: 147194

Other (OTH) AF: 0.422 AC: 6288 AN: 14884

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

African (AFR) AF: 0.842 AC: 34973 AN: 41512

American (AMR) AF: 0.485 AC: 7410 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1845 AN: 5156

South Asian (SAS) AF: 0.551 AC: 2657 AN: 4822

European-Finnish (FIN) AF: 0.286 AC: 3033 AN: 10590

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25966 AN: 67962

Other (OTH) AF: 0.483 AC: 1020 AN: 2110

Alfa AF: 0.435 Hom.: 46479

Bravo AF: 0.544

Asia WGS AF: 0.539 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.63
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10415576; hg19: chr19-50164390;