12-11650099-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_001987.5(ETV6):c.-29G>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.0000571 in 1,612,134 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000058 ( 1 hom. )
Consequence
ETV6
NM_001987.5 5_prime_UTR
NM_001987.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.27
Genes affected
ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000582 (85/1460050) while in subpopulation NFE AF= 0.000072 (80/1110444). AF 95% confidence interval is 0.0000589. There are 1 homozygotes in gnomad4_exome. There are 39 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETV6 | NM_001987.5 | c.-29G>A | 5_prime_UTR_variant | 1/8 | ENST00000396373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETV6 | ENST00000396373.9 | c.-29G>A | 5_prime_UTR_variant | 1/8 | 1 | NM_001987.5 | P1 | ||
ETV6 | ENST00000541426.1 | n.156G>A | non_coding_transcript_exon_variant | 1/4 | 4 | ||||
ETV6 | ENST00000544715.1 | n.89G>A | non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152084Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250874Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135742
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GnomAD4 exome AF: 0.0000582 AC: 85AN: 1460050Hom.: 1 Cov.: 29 AF XY: 0.0000537 AC XY: 39AN XY: 726490
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 02, 2023 | Variant summary: ETV6 c.-29G>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 3.6e-05 in 250874 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-29G>A in individuals affected with Thrombocytopenia 5 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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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