chr16-85806868-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_001861.6(COX4I1):c.504G>A(p.Lys168=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000361 in 1,613,364 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00036 ( 4 hom. )
Consequence
COX4I1
NM_001861.6 synonymous
NM_001861.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.38
Genes affected
COX4I1 (HGNC:2265): (cytochrome c oxidase subunit 4I1) Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. It is a multi-subunit enzyme complex that couples the transfer of electrons from cytochrome c to molecular oxygen and contributes to a proton electrochemical gradient across the inner mitochondrial membrane. The complex consists of 13 mitochondrial- and nuclear-encoded subunits. The mitochondrially-encoded subunits perform the electron transfer and proton pumping activities. The functions of the nuclear-encoded subunits are unknown but they may play a role in the regulation and assembly of the complex. This gene encodes the nuclear-encoded subunit IV isoform 1 of the human mitochondrial respiratory chain enzyme. It is located at the 3' of the NOC4 (neighbor of COX4) gene in a head-to-head orientation, and shares a promoter with it. Pseudogenes related to this gene are located on chromosomes 13 and 14. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 16-85806868-G-A is Benign according to our data. Variant chr16-85806868-G-A is described in ClinVar as [Benign]. Clinvar id is 3049635.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
COX4I1 | NM_001861.6 | c.504G>A | p.Lys168= | synonymous_variant | 5/5 | ENST00000253452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
COX4I1 | ENST00000253452.8 | c.504G>A | p.Lys168= | synonymous_variant | 5/5 | 1 | NM_001861.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000407 AC: 62AN: 152252Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000835 AC: 209AN: 250332Hom.: 1 AF XY: 0.000791 AC XY: 107AN XY: 135352
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GnomAD4 exome AF: 0.000358 AC: 523AN: 1460994Hom.: 4 Cov.: 31 AF XY: 0.000355 AC XY: 258AN XY: 726728
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.000523 AC XY: 39AN XY: 74512
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
COX4I1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 23, 2019 | This variant is classified as 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