19-40700155-G-C

Position:

chr19-40700155-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024876.4(COQ8B):c.1055C>G(p.Thr352Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,614,150 control chromosomes in the GnomAD database, including 1,759 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 120 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1639 hom. )

Consequence

COQ8B
NM_024876.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.242

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033581555).

BP6

Variant 19-40700155-G-C is Benign according to our data. Variant chr19-40700155-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 380101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4886/152324) while in subpopulation NFE AF= 0.0478 (3249/68030). AF 95% confidence interval is 0.0464. There are 120 homozygotes in gnomad4. There are 2377 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 120 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ8B	NM_024876.4 linkuse as main transcript	c.1055C>G	p.Thr352Arg	missense_variant	12/15	ENST00000324464.8	NP_079152.3
COQ8B	NM_001142555.3 linkuse as main transcript	c.932C>G	p.Thr311Arg	missense_variant	11/14		NP_001136027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464.8 linkuse as main transcript	c.1055C>G	p.Thr352Arg	missense_variant	12/15	1	NM_024876.4	ENSP00000315118	P2	Q96D53-1

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4888

AN:

152206

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00827

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.0665

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.0496

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0478

Gnomad OTH

AF:

0.0387

GnomAD3 exomes

AF:

0.0336

AC:

8440

AN:

251352

Hom.:

179

AF XY:

0.0338

AC XY:

4593

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00647

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0654

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00490

Gnomad FIN exome

AF:

0.0491

Gnomad NFE exome

AF:

0.0492

Gnomad OTH exome

AF:

0.0419

GnomAD4 exome

AF:

0.0440

AC:

64352

AN:

1461826

Hom.:

1639

Cov.:

AF XY:

0.0426

AC XY:

30982

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00726

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0648

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00550

Gnomad4 FIN exome

AF:

0.0501

Gnomad4 NFE exome

AF:

0.0500

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0321

AC:

4886

AN:

152324

Hom.:

120

Cov.:

AF XY:

0.0319

AC XY:

2377

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00825

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.0665

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.0496

Gnomad4 NFE

AF:

0.0478

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0306

TwinsUK

AF:

0.0429

AC:

159

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.0533

AC:

458

ExAC

AF:

0.0334

AC:

4054

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0534

EpiControl

AF:

0.0506

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 23, 2016	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 25, 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

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Apr 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.038

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.20

DANN

Benign

0.34

DEOGEN2

Benign

0.0037

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

1.1

N;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.076

MPC

0.30

ClinPred

0.000020

GERP RS

1.4

Varity_R

0.047

gMVP

0.65

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