chr4-184399021-C-T
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002199.4(IRF2):c.588G>A(p.Pro196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000205 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
IRF2
NM_002199.4 synonymous
NM_002199.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.50
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 4-184399021-C-T is Benign according to our data. Variant chr4-184399021-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3110834.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.49 with no splicing effect.
BS2
High AC in GnomAd4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF2 | NM_002199.4 | c.588G>A | p.Pro196= | synonymous_variant | 7/9 | ENST00000393593.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF2 | ENST00000393593.8 | c.588G>A | p.Pro196= | synonymous_variant | 7/9 | 1 | NM_002199.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000210 AC: 32AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000212 AC: 53AN: 250286Hom.: 0 AF XY: 0.000229 AC XY: 31AN XY: 135310
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GnomAD4 exome AF: 0.000204 AC: 298AN: 1460912Hom.: 0 Cov.: 30 AF XY: 0.000191 AC XY: 139AN XY: 726800
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GnomAD4 genome AF: 0.000210 AC: 32AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74458
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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 submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at