Genetic Variant ENST00000601291.5:c.1330C>T (chr19-49659618-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000601291.5(IRF3):c.1330C>T(p.Pro444Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,443,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P444A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IRF3
ENST00000601291.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.256

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14394495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000601291.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRF3	NM_001571.6	MANE Select	c.*30C>T		3_prime_UTR	Exon 8 of 8	NP_001562.1	Q14653-1
IRF3	NM_001197122.2		c.1330C>T	p.Pro444Ser	missense	Exon 8 of 8	NP_001184051.1	Q14653-4
IRF3	NM_001197123.2		c.*30C>T		3_prime_UTR	Exon 8 of 8	NP_001184052.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRF3	ENST00000601291.5	TSL:1	c.1330C>T	p.Pro444Ser	missense	Exon 8 of 8	ENSP00000471896.1	Q14653-4
IRF3	ENST00000377139.8	TSL:1 MANE Select	c.*30C>T		3_prime_UTR	Exon 8 of 8	ENSP00000366344.3	Q14653-1
IRF3	ENST00000309877.11	TSL:1	c.*30C>T		3_prime_UTR	Exon 7 of 7	ENSP00000310127.6	Q14653-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000459

AC:

AN:

217724

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1443072

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

716438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32962

American (AMR)

AF:

0.00

AC:

AN:

40948

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25656

East Asian (EAS)

AF:

0.00

AC:

AN:

38650

South Asian (SAS)

AF:

0.00

AC:

AN:

84114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52294

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102988

Other (OTH)

AF:

0.00

AC:

AN:

59734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Benign

1.3

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0085

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.43

M_CAP

Benign

0.0037

MetaRNN

Benign

0.14

PhyloP100

0.26

PrimateAI

Benign

0.26

Vest4

0.15

MVP

1.0

MPC

0.87

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.073

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over