Genetic Variant INPP4A:c.949+56_949+57delAC (chr2-98544045-GCA-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001134225.2(INPP4A):c.949+56_949+57delAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,380,998 control chromosomes in the GnomAD database, including 32,293 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 4730 hom., cov: 24)

Exomes 𝑓: 0.25 ( 27563 hom. )

Consequence

INPP4A
NM_001134225.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

4 publications found

Variant links:

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

INPP4A Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

INPP4A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4A	NM_001134225.2 link	c.949+56_949+57delAC		intron_variant	Intron 11 of 24	ENST00000409851.8	NP_001127697.1	Q96PE3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8 link	c.949+39_949+40delCA		intron_variant	Intron 11 of 24	1	NM_001134225.2	ENSP00000386777.4		Q96PE3-3

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

37826

AN:

150268

Hom.:

4727

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.338

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.347

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.293

GnomAD2 exomes

AF:

0.320

AC:

34509

AN:

107972

AF XY:

0.323

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.393

Gnomad EAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.339

GnomAD4 exome

AF:

0.254

AC:

312148

AN:

1230620

Hom.:

27563

AF XY:

0.255

AC XY:

154833

AN XY:

606288

show subpopulations

African (AFR)

AF:

0.238

AC:

6619

AN:

27852

American (AMR)

AF:

0.297

AC:

9485

AN:

31942

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

7454

AN:

21712

East Asian (EAS)

AF:

0.298

AC:

9136

AN:

30654

South Asian (SAS)

AF:

0.274

AC:

19340

AN:

70560

European-Finnish (FIN)

AF:

0.214

AC:

8601

AN:

40246

Middle Eastern (MID)

AF:

0.315

AC:

1546

AN:

4906

European-Non Finnish (NFE)

AF:

0.248

AC:

236230

AN:

952212

Other (OTH)

AF:

0.272

AC:

13737

AN:

50536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

11063

22126

33188

44251

55314

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.252

AC:

37860

AN:

150378

Hom.:

4730

Cov.:

AF XY:

0.250

AC XY:

18386

AN XY:

73410

show subpopulations

African (AFR)

AF:

0.234

AC:

9540

AN:

40794

American (AMR)

AF:

0.277

AC:

4199

AN:

15136

Ashkenazi Jewish (ASJ)

AF:

0.338

AC:

1166

AN:

3452

East Asian (EAS)

AF:

0.295

AC:

1515

AN:

5132

South Asian (SAS)

AF:

0.294

AC:

1399

AN:

4754

European-Finnish (FIN)

AF:

0.200

AC:

2065

AN:

10304

Middle Eastern (MID)

AF:

0.349

AC:

102

AN:

292

European-Non Finnish (NFE)

AF:

0.253

AC:

17114

AN:

67522

Other (OTH)

AF:

0.291

AC:

607

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1435

2869

4304

5738

7173

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.188

Hom.:

390

Bravo

AF:

0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.5

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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2-98544045-GCACACACA-GCACACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over