Genetic Variant ITPK1:c.*4343G>A (chr14-92937218-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014216.6(ITPK1):c.*4343G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,162 control chromosomes in the GnomAD database, including 8,609 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 0.33 ( 8607 hom., cov: 33)

Exomes 𝑓: 0.45 ( 2 hom. )

Consequence

ITPK1
NM_014216.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

Publications

5 publications found

Variant links:

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]

ITPK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ITPK1	NM_014216.6	MANE Select	c.*4343G>A	3_prime_UTR	Exon 11 of 11	NP_055031.2
ITPK1	NM_001142593.3		c.*4343G>A	3_prime_UTR	Exon 11 of 11	NP_001136065.1
ITPK1	NM_001142594.3		c.*1265G>A	3_prime_UTR	Exon 11 of 11	NP_001136066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPK1	ENST00000267615.11	TSL:1 MANE Select	c.*4343G>A		3_prime_UTR	Exon 11 of 11	ENSP00000267615.5
	ITPK1	ENST00000354313.7	TSL:1	c.*1265G>A		3_prime_UTR	Exon 11 of 11	ENSP00000346272.3

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49702

AN:

152022

Hom.:

8607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.216

Gnomad EAS

AF:

0.695

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.455

AC:

AN:

Hom.:

Cov.:

AF XY:

0.429

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.375

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.327

AC:

49727

AN:

152140

Hom.:

8607

Cov.:

AF XY:

0.331

AC XY:

24653

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.347

AC:

14390

AN:

41488

American (AMR)

AF:

0.360

AC:

5506

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

750

AN:

3470

East Asian (EAS)

AF:

0.694

AC:

3596

AN:

5180

South Asian (SAS)

AF:

0.393

AC:

1895

AN:

4820

European-Finnish (FIN)

AF:

0.320

AC:

3387

AN:

10568

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19158

AN:

68004

Other (OTH)

AF:

0.307

AC:

649

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1708

3416

5123

6831

8539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.298

Hom.:

1172

Bravo

AF:

0.329

Asia WGS

AF:

0.518

AC:

1803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.69

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over