rs941536

Variant names:

• chr14-93095075-A-G
• rs941536
• NM_014216.6:c.96-18456T>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.96-18456T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,144 control chromosomes in the GnomAD database, including 555 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 0.061 (555 hom., cov: 33)
• Consequence: ITPK1 NM_014216.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPK1	NM_014216.6	c.96-18456T>C		intron_variant	Intron 2 of 10	ENST00000267615.11	NP_055031.2
ITPK1	NM_001142593.3	c.96-18456T>C		intron_variant	Intron 2 of 10		NP_001136065.1
ITPK1	NM_001142594.3	c.96-18456T>C		intron_variant	Intron 2 of 10		NP_001136066.1
ITPK1	XM_047431351.1	c.-238+19994T>C		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.96-18456T>C		intron_variant	Intron 2 of 10	1	NM_014216.6	ENSP00000267615.5

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 9213 AN: 152026 Hom.: 543 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.0964

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0222

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0164

Gnomad OTH AF: 0.0557

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

GnomAD4 genome AF: 0.0609 AC: 9268 AN: 152144 Hom.: 555 Cov.: 33 AF XY: 0.0604 AC XY: 4492 AN XY: 74396

African (AFR) AF: 0.143 AC: 5949 AN: 41482

American (AMR) AF: 0.0967 AC: 1479 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3468

East Asian (EAS) AF: 0.00464 AC: 24 AN: 5176

South Asian (SAS) AF: 0.0486 AC: 234 AN: 4816

European-Finnish (FIN) AF: 0.0222 AC: 235 AN: 10586

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0164 AC: 1115 AN: 68014

Other (OTH) AF: 0.0551 AC: 116 AN: 2106

Alfa AF: 0.0313 Hom.: 322

Bravo AF: 0.0725

Asia WGS AF: 0.0510 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.74
PhyloP100		-0.44
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: rs941536; hg19: chr14-93561420;