14-93095256-A-T

Position:

• chr14-93095256-A-T

Variant summary

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

The ENST00000267615.11(ITPK1):​c.96-18637T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,308 control chromosomes in the GnomAD database, including 338 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 0.050 (338 hom., cov: 33)
• Consequence: ITPK1 ENST00000267615.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.96-18637T>A		intron_variant		ENST00000267615.11	NP_055031.2
ITPK1	NM_001142593.3	c.96-18637T>A		intron_variant			NP_001136065.1
ITPK1	NM_001142594.3	c.96-18637T>A		intron_variant			NP_001136066.1
ITPK1	XM_047431351.1	c.-238+19813T>A		intron_variant			XP_047287307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11	c.96-18637T>A		intron_variant		1	NM_014216.6	ENSP00000267615.5

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7552 AN: 152190 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0499 AC: 7596 AN: 152308 Hom.: 338 Cov.: 33 AF XY: 0.0502 AC XY: 3737 AN XY: 74478

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.00404

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0222

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.00534 Hom.: 1

Bravo AF: 0.0595

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.33

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: rs744479; hg19: chr14-93561601;