rs4905043

chr14-93083664-G-Achr14-93083664-G-C

Variant summary

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

The NM_014216.6(ITPK1):c.96-7045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,912 control chromosomes in the GnomAD database, including 9,950 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 0.35 (9950 hom., cov: 32)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79

Genes affected

ITPK1 (HGNC:6177): (inositol-tetrakisphosphate 1-kinase) This gene encodes an enzyme that belongs to the inositol 1,3,4-trisphosphate 5/6-kinase family. This enzyme regulates the synthesis of inositol tetraphosphate, and downstream products, inositol pentakisphosphate and inositol hexakisphosphate. Inositol metabolism plays a role in the development of the neural tube. Disruptions in this gene are thought to be associated with neural tube defects. A pseudogene of this gene has been identified on chromosome X. [provided by RefSeq, Jul 2016]

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 (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITPK1	NM_014216.6	c.96-7045C>T		intron_variant		ENST00000267615.11
ITPK1	NM_001142593.3	c.96-7045C>T		intron_variant
ITPK1	NM_001142594.3	c.96-7045C>T		intron_variant
ITPK1	XM_047431351.1	c.-238+31405C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITPK1	ENST00000267615.11	c.96-7045C>T		intron_variant		1	NM_014216.6	P1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53554 AN: 151794 Hom.: 9944 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.353 AC: 53606 AN: 151912 Hom.: 9950 Cov.: 32 AF XY: 0.356 AC XY: 26448 AN XY: 74224

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.336

Alfa AF: 0.381 Hom.: 14691

Bravo AF: 0.350

Asia WGS AF: 0.456 AC: 1583 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	0.027
Dann	Benign	0.36

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: rs4905043; hg19: chr14-93550009;