Variant chr19-40692025-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024876.4(COQ8B):c.*10T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,589,246 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 18 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 28 hom. )

Consequence

COQ8B
NM_024876.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.297

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 (BayesDel_noAF=-0.83).

BP6

Variant 19-40692025-A-G is Benign according to our data. Variant chr19-40692025-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 385429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00902 (1373/152196) while in subpopulation AFR AF= 0.03 (1247/41526). AF 95% confidence interval is 0.0286. There are 18 homozygotes in gnomad4. There are 652 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COQ8B	NM_024876.4 link	c.*10T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000324464.8	NP_079152.3	Q96D53-1
COQ8B	NM_001142555.3 link	c.*10T>C		3_prime_UTR_variant	Exon 14 of 14		NP_001136027.1	Q96D53-2A0A024R0Q9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464 link	c.*10T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_024876.4	ENSP00000315118.3		Q96D53-1

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1370

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00329

AC:

699

AN:

212696

Hom.:

AF XY:

0.00275

AC XY:

317

AN XY:

115120

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.00138

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000371

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000224

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00151

AC:

2164

AN:

1437050

Hom.:

Cov.:

AF XY:

0.00138

AC XY:

983

AN XY:

712550

show subpopulations

Gnomad4 AFR exome

AF:

0.0321

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000362

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000234

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.00902

AC:

1373

AN:

152196

Hom.:

Cov.:

AF XY:

0.00876

AC XY:

652

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0300

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00797

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 12, 2016

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. -

Nephrotic syndrome, type 9

Benign:1

Oct 08, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.2

DANN

Benign

0.60

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