chr14-93095256-A-T

Variant names:

• chr14-93095256-A-T
• rs744479
• NM_014216.6:c.96-18637T>A

Variant summary

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

The NM_014216.6(ITPK1):​c.96-18637T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 152,308 control chromosomes in the GnomAD database, including 338 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 0.050 (338 hom., cov: 33)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	NM_014216.6	MANE Select	c.96-18637T>A		intron	N/A	NP_055031.2
	ITPK1	NM_001142593.3		c.96-18637T>A		intron	N/A	NP_001136065.1	Q13572-1
	ITPK1	NM_001142594.3		c.96-18637T>A		intron	N/A	NP_001136066.1	Q13572-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	ENST00000267615.11	TSL:1 MANE Select	c.96-18637T>A		intron	N/A	ENSP00000267615.5	Q13572-1
	ITPK1	ENST00000556603.6	TSL:1	c.96-18637T>A		intron	N/A	ENSP00000451091.1	Q13572-1
	ITPK1	ENST00000354313.7	TSL:1	c.96-18637T>A		intron	N/A	ENSP00000346272.3	Q13572-2

Frequencies

GnomAD3 genomes AF: 0.0496 AC: 7552 AN: 152190 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0499 AC: 7596 AN: 152308 Hom.: 338 Cov.: 33 AF XY: 0.0502 AC XY: 3737 AN XY: 74478

African (AFR) AF: 0.107 AC: 4446 AN: 41552

American (AMR) AF: 0.0896 AC: 1371 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3468

East Asian (EAS) AF: 0.00404 AC: 21 AN: 5192

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4828

European-Finnish (FIN) AF: 0.0222 AC: 236 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0162 AC: 1102 AN: 68024

Other (OTH) AF: 0.0445 AC: 94 AN: 2114

Alfa AF: 0.00534 Hom.: 1

Bravo AF: 0.0595

Asia WGS AF: 0.0450 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.49
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: rs744479; hg19: chr14-93561601;