rs2288450

Positions:

• chr19-40703272-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024876.4(COQ8B):​c.799+269G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 449,214 control chromosomes in the GnomAD database, including 3,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1026 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2337 hom.)
• Consequence: COQ8B NM_024876.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.399

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-40703272-C-T is Benign according to our data. Variant chr19-40703272-C-T is described in ClinVar as [Benign]. Clinvar id is 671728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8B	NM_024876.4	c.799+269G>A		intron_variant		ENST00000324464.8
COQ8B	NM_001142555.3	c.676+269G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8B	ENST00000324464.8	c.799+269G>A		intron_variant		1	NM_024876.4	P2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15538 AN: 152050 Hom.: 1024 Cov.: 32

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.120 AC: 35648 AN: 297046 Hom.: 2337 AF XY: 0.120 AC XY: 18572 AN XY: 154276

Gnomad4 AFR exome AF: 0.0301

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.102 AC: 15547 AN: 152168 Hom.: 1026 Cov.: 32 AF XY: 0.104 AC XY: 7700 AN XY: 74376

Gnomad4 AFR AF: 0.0329

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0731

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.124 Hom.: 265

Bravo AF: 0.0976

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2288450; hg19: chr19-41209177;