rs8006385

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014216.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	NM_014216.6	MANE Select	c.121-17880T>C		intron	N/A	NP_055031.2
	ITPK1	NM_001142593.3		c.121-17880T>C		intron	N/A	NP_001136065.1
	ITPK1	NM_001142594.3		c.121-17880T>C		intron	N/A	NP_001136066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	ENST00000267615.11	TSL:1 MANE Select	c.121-17880T>C		intron	N/A	ENSP00000267615.5
	ITPK1	ENST00000556603.6	TSL:1	c.121-17880T>C		intron	N/A	ENSP00000451091.1
	ITPK1	ENST00000354313.7	TSL:1	c.121-17880T>C		intron	N/A	ENSP00000346272.3

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

African (AFR) AF: 0.172 AC: 7143 AN: 41554

American (AMR) AF: 0.108 AC: 1649 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 500 AN: 3470

East Asian (EAS) AF: 0.0775 AC: 401 AN: 5172

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4830

European-Finnish (FIN) AF: 0.0966 AC: 1026 AN: 10616

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7622 AN: 68012

Other (OTH) AF: 0.137 AC: 290 AN: 2116

Alfa AF: 0.118 Hom.: 3230

Bravo AF: 0.131

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.78
PhyloP100		0.047
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: rs8006385; hg19: chr14-93501026;