chr19-40703272-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024876.4(COQ8B):​c.799+269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 449,214 control chromosomes in the GnomAD database, including 3,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1026 hom., cov: 32)
Exomes 𝑓: 0.12 ( 2337 hom. )

Consequence

COQ8B
NM_024876.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.399

Publications

6 publications found
Variant links:
Genes affected
COQ8B (HGNC:19041): (coenzyme Q8B) This gene encodes a protein with two copies of a domain found in protein kinases. The encoded protein has a complete protein kinase catalytic domain, and a truncated domain that contains only the active and binding sites of the protein kinase domain, however, it is not known whether the protein has any kinase activity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
COQ8B Gene-Disease associations (from GenCC):
  • mitochondrial disease
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • nephrotic syndrome, type 9
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • familial idiopathic steroid-resistant nephrotic syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 19-40703272-C-T is Benign according to our data. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-40703272-C-T is described in CliVar as Benign. Clinvar id is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COQ8BNM_024876.4 linkc.799+269G>A intron_variant Intron 9 of 14 ENST00000324464.8 NP_079152.3 Q96D53-1
COQ8BNM_001142555.3 linkc.676+269G>A intron_variant Intron 8 of 13 NP_001136027.1 Q96D53-2A0A024R0Q9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COQ8BENST00000324464.8 linkc.799+269G>A intron_variant Intron 9 of 14 1 NM_024876.4 ENSP00000315118.3 Q96D53-1

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15538
AN:
152050
Hom.:
1024
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0330
Gnomad AMI
AF:
0.0274
Gnomad AMR
AF:
0.143
Gnomad ASJ
AF:
0.113
Gnomad EAS
AF:
0.0731
Gnomad SAS
AF:
0.116
Gnomad FIN
AF:
0.150
Gnomad MID
AF:
0.105
Gnomad NFE
AF:
0.129
Gnomad OTH
AF:
0.101
GnomAD4 exome
AF:
0.120
AC:
35648
AN:
297046
Hom.:
2337
AF XY:
0.120
AC XY:
18572
AN XY:
154276
show subpopulations
African (AFR)
AF:
0.0301
AC:
270
AN:
8974
American (AMR)
AF:
0.165
AC:
1598
AN:
9702
Ashkenazi Jewish (ASJ)
AF:
0.100
AC:
988
AN:
9880
East Asian (EAS)
AF:
0.130
AC:
2738
AN:
20988
South Asian (SAS)
AF:
0.114
AC:
2852
AN:
25066
European-Finnish (FIN)
AF:
0.145
AC:
2902
AN:
19988
Middle Eastern (MID)
AF:
0.115
AC:
166
AN:
1440
European-Non Finnish (NFE)
AF:
0.121
AC:
22099
AN:
183082
Other (OTH)
AF:
0.114
AC:
2035
AN:
17926
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1457
2914
4371
5828
7285
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
158
316
474
632
790
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.102
AC:
15547
AN:
152168
Hom.:
1026
Cov.:
32
AF XY:
0.104
AC XY:
7700
AN XY:
74376
show subpopulations
African (AFR)
AF:
0.0329
AC:
1365
AN:
41532
American (AMR)
AF:
0.143
AC:
2190
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.113
AC:
392
AN:
3470
East Asian (EAS)
AF:
0.0731
AC:
378
AN:
5170
South Asian (SAS)
AF:
0.117
AC:
564
AN:
4820
European-Finnish (FIN)
AF:
0.150
AC:
1589
AN:
10588
Middle Eastern (MID)
AF:
0.110
AC:
32
AN:
292
European-Non Finnish (NFE)
AF:
0.129
AC:
8804
AN:
67986
Other (OTH)
AF:
0.0986
AC:
208
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
720
1439
2159
2878
3598
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
178
356
534
712
890
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.124
Hom.:
265
Bravo
AF:
0.0976
Asia WGS
AF:
0.0880
AC:
307
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 19, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
2.4
DANN
Benign
0.60
PhyloP100
-0.40
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs2288450; hg19: chr19-41209177; API