chr4-184388899-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002199.4(IRF2):​c.909C>T​(p.Ser303=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,614,068 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 83 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 79 hom. )

Consequence

IRF2
NM_002199.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.73
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 -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 4-184388899-G-A is Benign according to our data. Variant chr4-184388899-G-A is described in ClinVar as [Benign]. Clinvar id is 708814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.73 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRF2NM_002199.4 linkuse as main transcriptc.909C>T p.Ser303= synonymous_variant 9/9 ENST00000393593.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRF2ENST00000393593.8 linkuse as main transcriptc.909C>T p.Ser303= synonymous_variant 9/91 NM_002199.4 P1P14316-1

Frequencies

GnomAD3 genomes
AF:
0.0180
AC:
2744
AN:
152056
Hom.:
84
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0630
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00707
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.0115
GnomAD3 exomes
AF:
0.00468
AC:
1177
AN:
251276
Hom.:
39
AF XY:
0.00350
AC XY:
476
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0650
Gnomad AMR exome
AF:
0.00278
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:
0.0000881
Gnomad OTH exome
AF:
0.00212
GnomAD4 exome
AF:
0.00179
AC:
2617
AN:
1461894
Hom.:
79
Cov.:
30
AF XY:
0.00154
AC XY:
1119
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0645
Gnomad4 AMR exome
AF:
0.00322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.00382
GnomAD4 genome
AF:
0.0181
AC:
2751
AN:
152174
Hom.:
83
Cov.:
32
AF XY:
0.0176
AC XY:
1311
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0629
Gnomad4 AMR
AF:
0.00706
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.0114
Alfa
AF:
0.0105
Hom.:
22
Bravo
AF:
0.0211
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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
-0.36
CADD
Benign
9.7
DANN
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs59219184; hg19: chr4-185310053; API