chr8-127738655-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_002467.6(MYC):c.438G>A(p.Gln146=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,020 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 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
MYC
NM_002467.6 synonymous
NM_002467.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.26
Genes affected
MYC (HGNC:7553): (MYC proto-oncogene, bHLH transcription factor) This gene is a proto-oncogene and encodes a nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. The encoded protein forms a heterodimer with the related transcription factor MAX. This complex binds to the E box DNA consensus sequence and regulates the transcription of specific target genes. Amplification of this gene is frequently observed in numerous human cancers. Translocations involving this gene are associated with Burkitt lymphoma and multiple myeloma in human patients. There is evidence to show that translation initiates both from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site, resulting in the production of two isoforms with distinct N-termini. [provided by RefSeq, Aug 2017]
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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=-0.51).
BP6
?
Variant 8-127738655-G-A is Benign according to our data. Variant chr8-127738655-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3058659.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=3.26 with no splicing effect.
BS2
?
High AC in GnomAdExome at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYC | NM_002467.6 | c.438G>A | p.Gln146= | synonymous_variant | 2/3 | ENST00000621592.8 | |
MYC | NM_001354870.1 | c.435G>A | p.Gln145= | synonymous_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYC | ENST00000621592.8 | c.438G>A | p.Gln146= | synonymous_variant | 2/3 | 1 | NM_002467.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251212Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135786
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727130
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74468
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MYC-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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