chr19-40720510-C-G

Position:

• chr19-40720510-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025194.3(ITPKC):​c.1155+2220C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,708 control chromosomes in the GnomAD database, including 32,913 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 0.65 (32913 hom., cov: 29)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKC	NM_025194.3	c.1155+2220C>G		intron_variant		ENST00000263370.3	NP_079470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPKC	ENST00000263370.3	c.1155+2220C>G		intron_variant		1	NM_025194.3	ENSP00000263370.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99005 AN: 151590 Hom.: 32867 Cov.: 29

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.625

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.653 AC: 99107 AN: 151708 Hom.: 32913 Cov.: 29 AF XY: 0.655 AC XY: 48525 AN XY: 74106

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.626

Alfa AF: 0.621 Hom.: 3471

Bravo AF: 0.661

Asia WGS AF: 0.694 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.30

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: rs2561528; hg19: chr19-41226415;