rs4905043

Variant names:

• chr14-93083664-G-A
• rs4905043
• NM_014216.6:c.96-7045C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-93083664-G-A
• chr14-93083664-G-C

Variant summary

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

The ENST00000267615.11(ITPK1):​c.96-7045C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,912 control chromosomes in the GnomAD database, including 9,950 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 0.35 (9950 hom., cov: 32)
• Consequence: ITPK1 ENST00000267615.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.79
• Publications: 4 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 (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000267615.11. 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.96-7045C>T		intron	N/A	NP_055031.2
	ITPK1	NM_001142593.3		c.96-7045C>T		intron	N/A	NP_001136065.1
	ITPK1	NM_001142594.3		c.96-7045C>T		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.96-7045C>T		intron	N/A	ENSP00000267615.5
	ITPK1	ENST00000556603.6	TSL:1	c.96-7045C>T		intron	N/A	ENSP00000451091.1
	ITPK1	ENST00000354313.7	TSL:1	c.96-7045C>T		intron	N/A	ENSP00000346272.3

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53554 AN: 151794 Hom.: 9944 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.353 AC: 53606 AN: 151912 Hom.: 9950 Cov.: 32 AF XY: 0.356 AC XY: 26448 AN XY: 74224

African (AFR) AF: 0.229 AC: 9474 AN: 41444

American (AMR) AF: 0.442 AC: 6760 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2110 AN: 5128

South Asian (SAS) AF: 0.481 AC: 2311 AN: 4808

European-Finnish (FIN) AF: 0.370 AC: 3903 AN: 10544

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26634 AN: 67924

Other (OTH) AF: 0.336 AC: 709 AN: 2110

Alfa AF: 0.380 Hom.: 17282

Bravo AF: 0.350

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.027
DANN	Benign	0.36
PhyloP100		-2.8
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: rs4905043; hg19: chr14-93550009;