rs2281515

Positions:

• chr14-92937218-C-T

Variant summary

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

The NM_014216.6(ITPK1):​c.*4343G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,162 control chromosomes in the GnomAD database, including 8,609 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 0.33 (8607 hom., cov: 33)
  • Exomes 𝑓: 0.45 (2 hom.)
• Consequence: ITPK1 NM_014216.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.*4343G>A		3_prime_UTR_variant	11/11	ENST00000267615.11	NP_055031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11	c.*4343G>A		3_prime_UTR_variant	11/11	1	NM_014216.6	ENSP00000267615	P1
ITPK1	ENST00000354313.7	c.*1265G>A		3_prime_UTR_variant	11/11	1		ENSP00000346272

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49702 AN: 152022 Hom.: 8607 Cov.: 33

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 2 Cov.: 0 AF XY: 0.429 AC XY: 6 AN XY: 14

Gnomad4 FIN exome AF: 0.375

Gnomad4 OTH exome AF: 0.667

GnomAD4 genome AF: 0.327 AC: 49727 AN: 152140 Hom.: 8607 Cov.: 33 AF XY: 0.331 AC XY: 24653 AN XY: 74376

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.307

Alfa AF: 0.297 Hom.: 1135

Bravo AF: 0.329

Asia WGS AF: 0.518 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.69

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: rs2281515; hg19: chr14-93403563;