19-40691898-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_024876.4(COQ8B):c.*137G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 809,908 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (14 hom.)
• Consequence: COQ8B NM_024876.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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=-0.58).
• BP6: Variant 19-40691898-C-T is Benign according to our data. Variant chr19-40691898-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1905/152242) while in subpopulation AFR AF= 0.0427 (1772/41526). AF 95% confidence interval is 0.041. There are 46 homozygotes in gnomad4. There are 905 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8B	NM_024876.4	c.*137G>A		3_prime_UTR_variant	15/15	ENST00000324464.8
COQ8B	NM_001142555.3	c.*137G>A		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8B	ENST00000324464.8	c.*137G>A		3_prime_UTR_variant	15/15	1	NM_024876.4	P2

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1902 AN: 152124 Hom.: 46 Cov.: 31

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00642

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00130 AC: 853 AN: 657666 Hom.: 14 Cov.: 9 AF XY: 0.00113 AC XY: 364 AN XY: 323244

Gnomad4 AFR exome AF: 0.0441

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000475

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000371

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.0125 AC: 1905 AN: 152242 Hom.: 46 Cov.: 31 AF XY: 0.0122 AC XY: 905 AN XY: 74446

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00978 Hom.: 0

Bravo AF: 0.0154

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.4
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs79441132; hg19: chr19-41197803;