chr19-40715608-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

COQ8B Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• nephrotic syndrome, type 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8B	NM_024876.4	MANE Select	c.-3-973C>G		intron	N/A	NP_079152.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8B	ENST00000324464.8	TSL:1 MANE Select	c.-3-973C>G		intron	N/A	ENSP00000315118.3	Q96D53-1
	COQ8B	ENST00000678404.1		c.-287C>G		5_prime_UTR	Exon 1 of 15	ENSP00000503944.1	Q96D53-1
	COQ8B	ENST00000871652.1		c.-54C>G		5_prime_UTR	Exon 1 of 15	ENSP00000541711.1

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

African (AFR) AF: 0.286 AC: 4515 AN: 15786

American (AMR) AF: 0.630 AC: 621 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 2027 AN: 5150

East Asian (EAS) AF: 0.491 AC: 1782 AN: 3630

South Asian (SAS) AF: 0.514 AC: 8479 AN: 16498

European-Finnish (FIN) AF: 0.532 AC: 167 AN: 314

Middle Eastern (MID) AF: 0.412 AC: 667 AN: 1620

European-Non Finnish (NFE) AF: 0.470 AC: 358299 AN: 761680

Other (OTH) AF: 0.472 AC: 12876 AN: 27300

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

African (AFR) AF: 0.308 AC: 12726 AN: 41274

American (AMR) AF: 0.549 AC: 8371 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1406 AN: 3466

East Asian (EAS) AF: 0.495 AC: 2539 AN: 5134

South Asian (SAS) AF: 0.509 AC: 2445 AN: 4808

European-Finnish (FIN) AF: 0.533 AC: 5584 AN: 10468

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31907 AN: 67892

Other (OTH) AF: 0.449 AC: 944 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		-0.39
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4802085; hg19: chr19-41221513;