dbSNP rs2304205: IRF3:c.-48T>G (chr19-49665670-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001571.6(IRF3):c.-48T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,031,916 control chromosomes in the GnomAD database, including 42,351 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 0.36 ( 11519 hom., cov: 32)

Exomes 𝑓: 0.26 ( 30832 hom. )

Consequence

IRF3
NM_001571.6 5_prime_UTR

Scores

Splicing: ADA: 0.0001454

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.644

Variant links:

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 links:

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

BCL2L12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRF3	NM_001571.6 link	c.-48T>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000377139.8	NP_001562.1	Q14653-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRF3	ENST00000377139.8 link	c.-48T>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_001571.6	ENSP00000366344.3		Q14653-1

Frequencies

GnomAD3 genomes

AF:

0.358

AC:

54243

AN:

151442

Hom.:

11485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.190

Gnomad SAS

AF:

0.311

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.323

GnomAD4 exome

AF:

0.256

AC:

225605

AN:

880358

Hom.:

30832

Cov.:

AF XY:

0.258

AC XY:

113748

AN XY:

441416

show subpopulations

Gnomad4 AFR exome

AF:

0.610

Gnomad4 AMR exome

AF:

0.302

Gnomad4 ASJ exome

AF:

0.241

Gnomad4 EAS exome

AF:

0.187

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.226

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.275

GnomAD4 genome

AF:

0.358

AC:

54330

AN:

151558

Hom.:

11519

Cov.:

AF XY:

0.353

AC XY:

26115

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.606

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.238

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.310

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.224

Hom.:

1081

Bravo

AF:

0.374

Asia WGS

AF:

0.346

AC:

1198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over