chr19-49660812-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000601291.5(IRF3):​c.1015G>A​(p.Gly339Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,602,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

IRF3
ENST00000601291.5 missense

Scores

10

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant 19-49660812-C-T is Benign according to our data. Variant chr19-49660812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3286525.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRF3NM_001571.6 linkuse as main transcriptc.999G>A p.Thr333= synonymous_variant 7/8 ENST00000377139.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRF3ENST00000377139.8 linkuse as main transcriptc.999G>A p.Thr333= synonymous_variant 7/81 NM_001571.6 P1Q14653-1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152124
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000348
AC:
8
AN:
230052
Hom.:
0
AF XY:
0.0000404
AC XY:
5
AN XY:
123790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000313
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000292
Gnomad SAS exome
AF:
0.0000361
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000968
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1450824
Hom.:
0
Cov.:
30
AF XY:
0.0000111
AC XY:
8
AN XY:
720456
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000233
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000203
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000632
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152124
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000416
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 12, 2024This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
8.3
DANN
Benign
0.88
FATHMM_MKL
Benign
0.023
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.056
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
Sift4G
Benign
0.14
T
Vest4
0.14
MVP
0.76
MPC
0.45
GERP RS
-9.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.35
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.35
Position offset: -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.

Other links and lift over

dbSNP: rs758305171; hg19: chr19-50164069; COSMIC: COSV55865558; COSMIC: COSV55865558; API