rs941578

Variant names:

• chr14-92960275-T-C
• rs941578
• NM_014216.6:c.505-1909A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014216.6(ITPK1):​c.505-1909A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,060 control chromosomes in the GnomAD database, including 2,294 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 0.15 (2294 hom., cov: 33)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.505-1909A>G		intron_variant	Intron 7 of 10	ENST00000267615.11	NP_055031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11	c.505-1909A>G		intron_variant	Intron 7 of 10	1	NM_014216.6	ENSP00000267615.5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22706 AN: 151942 Hom.: 2289 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0915

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.150 AC: 22742 AN: 152060 Hom.: 2294 Cov.: 33 AF XY: 0.145 AC XY: 10798 AN XY: 74346

African (AFR) AF: 0.284 AC: 11766 AN: 41438

American (AMR) AF: 0.0914 AC: 1397 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0950 AC: 330 AN: 3472

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5170

South Asian (SAS) AF: 0.0753 AC: 363 AN: 4822

European-Finnish (FIN) AF: 0.0745 AC: 789 AN: 10594

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7585 AN: 67954

Other (OTH) AF: 0.133 AC: 282 AN: 2114

Alfa AF: 0.117 Hom.: 1998

Bravo AF: 0.156

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.66
DANN	Benign	0.72
PhyloP100		-1.1
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: rs941578; hg19: chr14-93426620;