chr19-42248542-GC-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PVS1_Moderate
The NM_006494.4(ERF):c.1569del(p.Leu525SerfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,396,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
ERF
NM_006494.4 frameshift
NM_006494.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.719
Genes affected
ERF (HGNC:3444): (ETS2 repressor factor) ETS2 is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase. The protein encoded by this gene binds to the ETS2 promoter and is a strong repressor of ETS2 transcription. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0474 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERF | NM_006494.4 | c.1569del | p.Leu525SerfsTer6 | frameshift_variant | 4/4 | ENST00000222329.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERF | ENST00000222329.9 | c.1569del | p.Leu525SerfsTer6 | frameshift_variant | 4/4 | 1 | NM_006494.4 | P1 | |
ERF | ENST00000440177.6 | c.1344del | p.Leu450SerfsTer6 | frameshift_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.0000186 AC: 26AN: 1396630Hom.: 0 Cov.: 32 AF XY: 0.0000276 AC XY: 19AN XY: 689384
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1396630
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32
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19
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689384
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 08, 2017 | The c.1569delG variant in the ERF gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1569delG variant causes a frameshift starting with codon Leucine 525, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Leu525SerfsX6. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1569delG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1569delG as a variant of uncertain significance. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at