7-56102913-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_016139.4(CHCHD2):c.399C>T(p.Leu133Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,066 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 (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
CHCHD2
NM_016139.4 synonymous
NM_016139.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.896
Genes affected
CHCHD2 (HGNC:21645): (coiled-coil-helix-coiled-coil-helix domain containing 2) The protein encoded by this gene belongs to a class of eukaryotic CX(9)C proteins characterized by four cysteine residues spaced ten amino acids apart from one another. These residues form disulfide linkages that define a CHCH fold. In response to stress, the protein translocates from the mitochondrial intermembrane space to the nucleus where it binds to a highly conserved 13 nucleotide oxygen responsive element in the promoter of cytochrome oxidase 4I2, a subunit of the terminal enzyme of the electron transport chain. In concert with recombination signal sequence-binding protein J, binding of this protein activates the oxygen responsive element at four percent oxygen. In addition, it has been shown that this protein is a negative regulator of mitochondria-mediated apoptosis. In response to apoptotic stimuli, mitochondrial levels of this protein decrease, allowing BCL2-associated X protein to oligomerize and activate the caspase cascade. Pseudogenes of this gene are found on multiple chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 7-56102913-G-A is Benign according to our data. Variant chr7-56102913-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040964.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=0.896 with no splicing effect.
BS2
High AC in GnomAdExome4 at 27 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251292Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135822
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GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461752Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18AN XY: 727188
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CHCHD2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 12, 2021 | 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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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