rs7251246

Positions:

• chr19-40721201-C-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+2911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,646 control chromosomes in the GnomAD database, including 16,612 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 0.46 (16612 hom., cov: 30)
• Consequence: ITPKC NM_025194.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPKC	NM_025194.3	c.1155+2911C>T		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+2911C>T		intron_variant		1	NM_025194.3	ENSP00000263370.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69155 AN: 151528 Hom.: 16595 Cov.: 30

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.468

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

GnomAD4 genome AF: 0.456 AC: 69193 AN: 151646 Hom.: 16612 Cov.: 30 AF XY: 0.462 AC XY: 34191 AN XY: 74074

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.470

Alfa AF: 0.466 Hom.: 2710

Bravo AF: 0.449

Asia WGS AF: 0.551 AC: 1916 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	2.5
DANN	Benign	0.35

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: rs7251246; hg19: chr19-41227106;