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GeneBe

16-85805047-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001861.6(COX4I1):c.184T>C(p.Leu62=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,614,128 control chromosomes in the GnomAD database, including 799,762 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.97 ( 72468 hom., cov: 32)
Exomes 𝑓: 1.0 ( 727294 hom. )

Consequence

COX4I1
NM_001861.6 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20
Variant links:
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 -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.2 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COX4I1NM_001861.6 linkuse as main transcriptc.184T>C p.Leu62= synonymous_variant 3/5 ENST00000253452.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COX4I1ENST00000253452.8 linkuse as main transcriptc.184T>C p.Leu62= synonymous_variant 3/51 NM_001861.6 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.975
AC:
148364
AN:
152198
Hom.:
72418
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.911
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.993
Gnomad ASJ
AF:
1.00
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.999
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
1.00
Gnomad NFE
AF:
1.00
Gnomad OTH
AF:
0.984
GnomAD3 exomes
AF:
0.994
AC:
249550
AN:
251138
Hom.:
124048
AF XY:
0.995
AC XY:
135214
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.911
Gnomad AMR exome
AF:
0.997
Gnomad ASJ exome
AF:
1.00
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
1.00
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
1.00
Gnomad OTH exome
AF:
0.997
GnomAD4 exome
AF:
0.997
AC:
1458052
AN:
1461812
Hom.:
727294
Cov.:
53
AF XY:
0.998
AC XY:
725537
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.906
Gnomad4 AMR exome
AF:
0.996
Gnomad4 ASJ exome
AF:
1.00
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
1.00
Gnomad4 FIN exome
AF:
1.00
Gnomad4 NFE exome
AF:
1.00
Gnomad4 OTH exome
AF:
0.994
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.975
AC:
148472
AN:
152316
Hom.:
72468
Cov.:
32
AF XY:
0.976
AC XY:
72681
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.911
Gnomad4 AMR
AF:
0.993
Gnomad4 ASJ
AF:
1.00
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.999
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
1.00
Gnomad4 OTH
AF:
0.984
Alfa
AF:
0.987
Hom.:
33408
Bravo
AF:
0.971
Asia WGS
AF:
0.997
AC:
3466
AN:
3478
EpiCase
AF:
1.00
EpiControl
AF:
1.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
6.1
Dann
Benign
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2599091; hg19: chr16-85838653; API