rs7251246

Variant names:

• chr19-40721201-C-T
• rs7251246
• NM_025194.3:c.1155+2911C>T

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+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
• Publications: 12 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 (SAS) allele frequency at 95% confidence interval = 0.565 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	NM_025194.3	MANE Select	c.1155+2911C>T		intron	N/A	NP_079470.1	Q96DU7
	ITPKC	NM_001411098.1		c.1155+2911C>T		intron	N/A	NP_001398027.1	A0A8V8TPP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPKC	ENST00000263370.3	TSL:1 MANE Select	c.1155+2911C>T		intron	N/A	ENSP00000263370.1	Q96DU7
	ITPKC	ENST00000699490.1		c.1155+2911C>T		intron	N/A	ENSP00000514401.1	Q96DU7
	ITPKC	ENST00000699489.1		c.1155+2911C>T		intron	N/A	ENSP00000514400.1	A0A8V8TPP3

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

African (AFR) AF: 0.311 AC: 12844 AN: 41326

American (AMR) AF: 0.557 AC: 8480 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1439 AN: 3468

East Asian (EAS) AF: 0.543 AC: 2794 AN: 5146

South Asian (SAS) AF: 0.584 AC: 2802 AN: 4802

European-Finnish (FIN) AF: 0.540 AC: 5662 AN: 10490

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33546 AN: 67888

Other (OTH) AF: 0.470 AC: 988 AN: 2102

Alfa AF: 0.461 Hom.: 2756

Bravo AF: 0.449

Asia WGS AF: 0.551 AC: 1916 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	2.5
DANN	Benign	0.35
PhyloP100		-0.0070
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: rs7251246; hg19: chr19-41227106;