rs8021497

Variant names:

• chr14-93101273-G-A
• rs8021497
• NM_014216.6:c.95+13796C>T

Variant summary

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

The NM_014216.6(ITPK1):​c.95+13796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,054 control chromosomes in the GnomAD database, including 6,190 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 0.27 (6190 hom., cov: 32)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.95+13796C>T		intron_variant	Intron 2 of 10	ENST00000267615.11	NP_055031.2
ITPK1	NM_001142593.3	c.95+13796C>T		intron_variant	Intron 2 of 10		NP_001136065.1
ITPK1	NM_001142594.3	c.95+13796C>T		intron_variant	Intron 2 of 10		NP_001136066.1
ITPK1	XM_047431351.1	c.-238+13796C>T		intron_variant	Intron 2 of 9		XP_047287307.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPK1	ENST00000267615.11	c.95+13796C>T		intron_variant	Intron 2 of 10	1	NM_014216.6	ENSP00000267615.5

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40390 AN: 151936 Hom.: 6174 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.266 AC: 40451 AN: 152054 Hom.: 6190 Cov.: 32 AF XY: 0.265 AC XY: 19679 AN XY: 74338

African (AFR) AF: 0.432 AC: 17923 AN: 41454

American (AMR) AF: 0.190 AC: 2910 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 928 AN: 3466

East Asian (EAS) AF: 0.145 AC: 747 AN: 5168

South Asian (SAS) AF: 0.280 AC: 1351 AN: 4828

European-Finnish (FIN) AF: 0.196 AC: 2067 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13715 AN: 67978

Other (OTH) AF: 0.275 AC: 580 AN: 2108

Alfa AF: 0.234 Hom.: 1100

Bravo AF: 0.271

Asia WGS AF: 0.243 AC: 842 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	8.4
DANN	Benign	0.54
PhyloP100		0.63
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: rs8021497; hg19: chr14-93567618;