14-92992300-T-G

Variant names:

• chr14-92992300-T-G
• rs11625123
• NM_014216.6:c.364+1580A>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.364+1580A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,062 control chromosomes in the GnomAD database, including 20,383 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 0.51 (20383 hom., cov: 32)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 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.364+1580A>C		intron	N/A	NP_055031.2
	ITPK1	NM_001142593.3		c.364+1580A>C		intron	N/A	NP_001136065.1	Q13572-1
	ITPK1	NM_001142594.3		c.364+1580A>C		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.364+1580A>C		intron	N/A	ENSP00000267615.5	Q13572-1
	ITPK1	ENST00000556603.6	TSL:1	c.364+1580A>C		intron	N/A	ENSP00000451091.1	Q13572-1
	ITPK1	ENST00000354313.7	TSL:1	c.364+1580A>C		intron	N/A	ENSP00000346272.3	Q13572-2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76864 AN: 151944 Hom.: 20340 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.506 AC: 76962 AN: 152062 Hom.: 20383 Cov.: 32 AF XY: 0.509 AC XY: 37833 AN XY: 74332

African (AFR) AF: 0.606 AC: 25132 AN: 41470

American (AMR) AF: 0.584 AC: 8933 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1168 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3948 AN: 5168

South Asian (SAS) AF: 0.471 AC: 2271 AN: 4822

European-Finnish (FIN) AF: 0.481 AC: 5089 AN: 10572

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28896 AN: 67954

Other (OTH) AF: 0.464 AC: 980 AN: 2110

Alfa AF: 0.462 Hom.: 2703

Bravo AF: 0.522

Asia WGS AF: 0.599 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.95
DANN	Benign	0.50
PhyloP100		-0.43
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: rs11625123; hg19: chr14-93458645;