rs8006385

Variant names:

• chr14-93034681-A-G
• rs8006385
• NM_014216.6:c.121-17880T>C

Variant summary

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

The NM_014216.6(ITPK1):​c.121-17880T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,286 control chromosomes in the GnomAD database, including 1,493 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 0.13 (1493 hom., cov: 33)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.121-17880T>C		intron_variant	Intron 3 of 10	ENST00000267615.11	NP_055031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11	c.121-17880T>C		intron_variant	Intron 3 of 10	1	NM_014216.6	ENSP00000267615.5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20032 AN: 152168 Hom.: 1485 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.132 AC: 20066 AN: 152286 Hom.: 1493 Cov.: 33 AF XY: 0.133 AC XY: 9877 AN XY: 74462

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.144

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.0966

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.137

Alfa AF: 0.116 Hom.: 897

Bravo AF: 0.131

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.78

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: rs8006385; hg19: chr14-93501026;