rs2288450

Variant names:

• chr19-40703272-C-T
• rs2288450
• NM_024876.4:c.799+269G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399
• 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 -20 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 VariationId is 671728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.138 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.799+269G>A		intron	N/A	NP_079152.3
	COQ8B	NM_001142555.3		c.676+269G>A		intron	N/A	NP_001136027.1	Q96D53-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COQ8B	ENST00000324464.8	TSL:1 MANE Select	c.799+269G>A		intron	N/A	ENSP00000315118.3	Q96D53-1
	COQ8B	ENST00000243583.10	TSL:1	c.676+269G>A		intron	N/A	ENSP00000243583.5	Q96D53-2
	COQ8B	ENST00000871658.1		c.844+269G>A		intron	N/A	ENSP00000541717.1

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

African (AFR) AF: 0.0301 AC: 270 AN: 8974

American (AMR) AF: 0.165 AC: 1598 AN: 9702

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 988 AN: 9880

East Asian (EAS) AF: 0.130 AC: 2738 AN: 20988

South Asian (SAS) AF: 0.114 AC: 2852 AN: 25066

European-Finnish (FIN) AF: 0.145 AC: 2902 AN: 19988

Middle Eastern (MID) AF: 0.115 AC: 166 AN: 1440

European-Non Finnish (NFE) AF: 0.121 AC: 22099 AN: 183082

Other (OTH) AF: 0.114 AC: 2035 AN: 17926

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

African (AFR) AF: 0.0329 AC: 1365 AN: 41532

American (AMR) AF: 0.143 AC: 2190 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3470

East Asian (EAS) AF: 0.0731 AC: 378 AN: 5170

South Asian (SAS) AF: 0.117 AC: 564 AN: 4820

European-Finnish (FIN) AF: 0.150 AC: 1589 AN: 10588

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8804 AN: 67986

Other (OTH) AF: 0.0986 AC: 208 AN: 2110

Alfa AF: 0.124 Hom.: 265

Bravo AF: 0.0976

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2288450;

hg19: chr19-41209177;