Menu
GeneBe

4-184390739-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_002199.4(IRF2):c.705G>A(p.Thr235=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,614,184 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 40 hom. )

Consequence

IRF2
NM_002199.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.571
Variant links:
Genes affected
IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-184390739-C-T is Benign according to our data. Variant chr4-184390739-C-T is described in ClinVar as [Benign]. Clinvar id is 785109.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.571 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1812/152308) while in subpopulation AFR AF= 0.0415 (1726/41564). AF 95% confidence interval is 0.0399. There are 39 homozygotes in gnomad4. There are 818 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1811 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRF2NM_002199.4 linkuse as main transcriptc.705G>A p.Thr235= synonymous_variant 8/9 ENST00000393593.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRF2ENST00000393593.8 linkuse as main transcriptc.705G>A p.Thr235= synonymous_variant 8/91 NM_002199.4 P1P14316-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0119
AC:
1811
AN:
152190
Hom.:
39
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0416
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00399
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00716
GnomAD3 exomes
AF:
0.00327
AC:
822
AN:
251464
Hom.:
13
AF XY:
0.00233
AC XY:
316
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.0453
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000105
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.00128
AC:
1875
AN:
1461876
Hom.:
40
Cov.:
31
AF XY:
0.00110
AC XY:
798
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0444
Gnomad4 AMR exome
AF:
0.00203
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000113
Gnomad4 OTH exome
AF:
0.00252
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0119
AC:
1812
AN:
152308
Hom.:
39
Cov.:
33
AF XY:
0.0110
AC XY:
818
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0415
Gnomad4 AMR
AF:
0.00399
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00709
Alfa
AF:
0.00588
Hom.:
9
Bravo
AF:
0.0139
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
Cadd
Benign
4.1
Dann
Benign
0.72
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs77140332; hg19: chr4-185311893; API