19-40692092-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_024876.4(COQ8B):c.1578C>T(p.Asp526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00805 in 1,608,906 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0097 ( 16 hom., cov: 31)

Exomes 𝑓: 0.0079 ( 120 hom. )

Consequence

COQ8B
NM_024876.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.985

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 19-40692092-G-A is Benign according to our data. Variant chr19-40692092-G-A is described in ClinVar as [Benign]. Clinvar id is 380448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.985 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00972 (1479/152212) while in subpopulation EAS AF= 0.0426 (220/5162). AF 95% confidence interval is 0.038. There are 16 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8B	NM_024876.4 linkuse as main transcript	c.1578C>T	p.Asp526=	synonymous_variant	15/15	ENST00000324464.8
COQ8B	NM_001142555.3 linkuse as main transcript	c.1455C>T	p.Asp485=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8B	ENST00000324464.8 linkuse as main transcript	c.1578C>T	p.Asp526=	synonymous_variant	15/15	1	NM_024876.4	P2	Q96D53-1

Frequencies

GnomAD3 genomes

AF:

0.00973

AC:

1480

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.0425

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0464

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00744

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0125

AC:

2968

AN:

237150

Hom.:

AF XY:

0.0120

AC XY:

1544

AN XY:

128862

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.0148

Gnomad EAS exome

AF:

0.0445

Gnomad SAS exome

AF:

0.000886

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.00900

Gnomad OTH exome

AF:

0.00832

GnomAD4 exome

AF:

0.00787

AC:

11465

AN:

1456694

Hom.:

120

Cov.:

AF XY:

0.00776

AC XY:

5619

AN XY:

724286

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00223

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.0396

Gnomad4 SAS exome

AF:

0.00135

Gnomad4 FIN exome

AF:

0.0436

Gnomad4 NFE exome

AF:

0.00573

Gnomad4 OTH exome

AF:

0.00879

GnomAD4 genome

AF:

0.00972

AC:

1479

AN:

152212

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

897

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00568

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.0426

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.0464

Gnomad4 NFE

AF:

0.00744

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00795

Hom.:

Bravo

AF:

0.00656

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 08, 2016

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. -

Kidney disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 01, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

Cadd

Benign

9.0

Dann

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over