Genetic Variant NM_024876.4:c.-3-973C>G (chr19-40715608-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024876.4(COQ8B):c.-3-973C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 984,558 control chromosomes in the GnomAD database, including 106,840 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 0.44 ( 15276 hom., cov: 30)

Exomes 𝑓: 0.47 ( 91564 hom. )

Consequence

COQ8B
NM_024876.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.393

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

COQ8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8B	NM_024876.4 link	c.-3-973C>G		intron_variant	Intron 1 of 14	ENST00000324464.8	NP_079152.3	Q96D53-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464.8 link	c.-3-973C>G		intron_variant	Intron 1 of 14	1	NM_024876.4	ENSP00000315118.3		Q96D53-1

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66506

AN:

151476

Hom.:

15263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.545

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.495

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.470

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.468

AC:

389433

AN:

832964

Hom.:

91564

Cov.:

AF XY:

0.469

AC XY:

180303

AN XY:

384706

show subpopulations

African (AFR)

AF:

0.286

AC:

4515

AN:

15786

American (AMR)

AF:

0.630

AC:

621

AN:

986

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

2027

AN:

5150

East Asian (EAS)

AF:

0.491

AC:

1782

AN:

3630

South Asian (SAS)

AF:

0.514

AC:

8479

AN:

16498

European-Finnish (FIN)

AF:

0.532

AC:

167

AN:

314

Middle Eastern (MID)

AF:

0.412

AC:

667

AN:

1620

European-Non Finnish (NFE)

AF:

0.470

AC:

358299

AN:

761680

Other (OTH)

AF:

0.472

AC:

12876

AN:

27300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

11307

22615

33922

45230

56537

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14554

29108

43662

58216

72770

<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:

0.439

AC:

66541

AN:

151594

Hom.:

15276

Cov.:

AF XY:

0.443

AC XY:

32774

AN XY:

74062

show subpopulations

African (AFR)

AF:

0.308

AC:

12726

AN:

41274

American (AMR)

AF:

0.549

AC:

8371

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1406

AN:

3466

East Asian (EAS)

AF:

0.495

AC:

2539

AN:

5134

South Asian (SAS)

AF:

0.509

AC:

2445

AN:

4808

European-Finnish (FIN)

AF:

0.533

AC:

5584

AN:

10468

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.470

AC:

31907

AN:

67892

Other (OTH)

AF:

0.449

AC:

944

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1832

3664

5495

7327

9159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.440

Hom.:

1817

Bravo

AF:

0.432

Asia WGS

AF:

0.510

AC:

1773

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.66

PhyloP100

-0.39

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over