19-40715608-G-C

Variant names:

• chr19-40715608-G-C
• rs4802085
• NM_024876.4:c.-3-973C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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 -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	c.-3-973C>G		intron_variant	Intron 1 of 14	ENST00000324464.8	NP_079152.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66506 AN: 151476 Hom.: 15263 Cov.: 30

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.: 33 AF XY: 0.469 AC XY: 180303 AN XY: 384706

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.630

Gnomad4 ASJ exome AF: 0.394

Gnomad4 EAS exome AF: 0.491

Gnomad4 SAS exome AF: 0.514

Gnomad4 FIN exome AF: 0.532

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.439 AC: 66541 AN: 151594 Hom.: 15276 Cov.: 30 AF XY: 0.443 AC XY: 32774 AN XY: 74062

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.449

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
DANN	Benign	0.66

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: rs4802085; hg19: chr19-41221513;