rs2561530

chr19-40718409-G-Achr19-40718409-G-Cchr19-40718409-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPKC	NM_025194.3	c.1155+119G>A		intron_variant		ENST00000263370.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPKC	ENST00000263370.3	c.1155+119G>A		intron_variant		1	NM_025194.3	P1

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

Gnomad4 AFR exome AF: 0.680

Gnomad4 AMR exome AF: 0.679

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.776

Gnomad4 SAS exome AF: 0.569

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.590

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

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.591

Alfa AF: 0.570 Hom.: 31050

Bravo AF: 0.619

Asia WGS AF: 0.658 AC: 2288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.2
Dann	Benign	0.74

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: rs2561530; hg19: chr19-41224314;