19-40692092-G-A

Position:

• chr19-40692092-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.985

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]

ACMG classification

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 GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COQ8B	NM_024876.4	c.1578C>T	p.Asp526=	synonymous_variant	15/15	ENST00000324464.8	NP_079152.3
COQ8B	NM_001142555.3	c.1455C>T	p.Asp485=	synonymous_variant	14/14		NP_001136027.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COQ8B	ENST00000324464.8	c.1578C>T	p.Asp526=	synonymous_variant	15/15	1	NM_024876.4	ENSP00000315118	P2

Frequencies

GnomAD3 genomes AF: 0.00973 AC: 1480 AN: 152094 Hom.: 16 Cov.: 31

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.: 62 AF XY: 0.0120 AC XY: 1544 AN XY: 128862

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.: 31 AF XY: 0.00776 AC XY: 5619 AN XY: 724286

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.: 16 Cov.: 31 AF XY: 0.0121 AC XY: 897 AN XY: 74406

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.: 6

Bravo AF: 0.00656

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

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

Other links and lift over

dbSNP: rs56276635; hg19: chr19-41197997;