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: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 (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	P1

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;