chr19-40718409-G-A

Variant names:

• chr19-40718409-G-A
• rs2561530
• NM_025194.3:c.1155+119G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025194.3(ITPKC):​c.1155+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,309,614 control chromosomes in the GnomAD database, including 225,359 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 0.62 (29232 hom., cov: 31)
  • Exomes 𝑓: 0.58 (196127 hom.)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 4 publications found

Genes affected

ITPKC (HGNC:14897): (inositol-trisphosphate 3-kinase C) This gene encodes a member of the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase family of enzymes that catalyze the phosphorylation of inositol 1,4,5-trisphosphate to 1,3,4,5-tetrakisphosphate. The encoded protein is localized to the nucleus and cytoplasm and has both nuclear import and nuclear export activity. Single nucleotide polymorphisms in this gene are associated with Kawasaki disease.[provided by RefSeq, Sep 2009]

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025194.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	NM_025194.3	MANE Select	c.1155+119G>A		intron	N/A	NP_079470.1
	ITPKC	NM_001411098.1		c.1155+119G>A		intron	N/A	NP_001398027.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.1155+119G>A		intron	N/A	ENSP00000263370.1
	ITPKC	ENST00000699490.1		c.1155+119G>A		intron	N/A	ENSP00000514401.1
	ITPKC	ENST00000699489.1		c.1155+119G>A		intron	N/A	ENSP00000514400.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93565 AN: 151800 Hom.: 29192 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.579 AC: 670112 AN: 1157696 Hom.: 196127 AF XY: 0.578 AC XY: 326145 AN XY: 563934

African (AFR) AF: 0.680 AC: 18373 AN: 27008

American (AMR) AF: 0.679 AC: 13540 AN: 19934

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 8941 AN: 17626

East Asian (EAS) AF: 0.776 AC: 27623 AN: 35592

South Asian (SAS) AF: 0.569 AC: 29040 AN: 51016

European-Finnish (FIN) AF: 0.665 AC: 19688 AN: 29594

Middle Eastern (MID) AF: 0.516 AC: 1692 AN: 3282

European-Non Finnish (NFE) AF: 0.565 AC: 522323 AN: 924676

Other (OTH) AF: 0.590 AC: 28892 AN: 48968

GnomAD4 genome AF: 0.617 AC: 93661 AN: 151918 Hom.: 29232 Cov.: 31 AF XY: 0.620 AC XY: 45995 AN XY: 74232

African (AFR) AF: 0.679 AC: 28100 AN: 41390

American (AMR) AF: 0.645 AC: 9836 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3742 AN: 5166

South Asian (SAS) AF: 0.574 AC: 2760 AN: 4812

European-Finnish (FIN) AF: 0.674 AC: 7131 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38343 AN: 67936

Other (OTH) AF: 0.591 AC: 1246 AN: 2110

Alfa AF: 0.579 Hom.: 85354

Bravo AF: 0.619

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		-0.38
PromoterAI		-0.0086	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: rs2561530; hg19: chr19-41224314;