19-40692025-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.297

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 -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 GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COQ8B	NM_024876.4	c.*10T>C		3_prime_UTR_variant	15/15	ENST00000324464.8
COQ8B	NM_001142555.3	c.*10T>C		3_prime_UTR_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COQ8B	ENST00000324464.8	c.*10T>C		3_prime_UTR_variant	15/15	1	NM_024876.4	P2

Frequencies

GnomAD3 genomes AF: 0.00901 AC: 1370 AN: 152078 Hom.: 18 Cov.: 31

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.: 11 AF XY: 0.00275 AC XY: 317 AN XY: 115120

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.: 28 Cov.: 31 AF XY: 0.00138 AC XY: 983 AN XY: 712550

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.: 18 Cov.: 31 AF XY: 0.00876 AC XY: 652 AN XY: 74402

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.: 7

Bravo AF: 0.0106

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 12, 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. -

Nephrotic syndrome, type 9 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 08, 2021

- -

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

Other links and lift over

dbSNP: rs61742811; hg19: chr19-41197930;