Genetic Variant PIP4P1:c.440+7G>A (chr14-20460185-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_144568.4(PIP4P1):c.440+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00734 in 1,611,152 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 59 hom. )

Consequence

PIP4P1
NM_144568.4 splice_region, intron

Scores

Splicing: ADA: 0.0001752

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

PIP4P1 (HGNC:19299): (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 1) TMEM55B catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) by removing the 4-phosphate (Ungewickell et al., 2005 [PubMed 16365287]).[supplied by OMIM, Mar 2008]

PIP4P1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 14-20460185-C-T is Benign according to our data. Variant chr14-20460185-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3341540.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PIP4P1	NM_144568.4 link	c.440+7G>A	splice_region_variant, intron_variant	Intron 3 of 6	ENST00000250489.9	NP_653169.2	Q86T03-1
PIP4P1	NM_001100814.3 link	c.461+7G>A	splice_region_variant, intron_variant	Intron 3 of 6		NP_001094284.1	Q86T03-2
PIP4P1	XM_024449739.2 link	c.461+7G>A	splice_region_variant, intron_variant	Intron 3 of 5		XP_024305507.1
PIP4P1	XM_024449740.2 link	c.440+7G>A	splice_region_variant, intron_variant	Intron 3 of 5		XP_024305508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP4P1	ENST00000250489.9 link	c.440+7G>A		splice_region_variant, intron_variant	Intron 3 of 6	1	NM_144568.4	ENSP00000250489.4		Q86T03-1

Frequencies

GnomAD3 genomes

AF:

0.00509

AC:

774

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00928

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00513

AC:

1290

AN:

251472

Hom.:

AF XY:

0.00528

AC XY:

718

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00283

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00415

Gnomad FIN exome

AF:

0.00402

Gnomad NFE exome

AF:

0.00822

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00758

AC:

11055

AN:

1458850

Hom.:

Cov.:

AF XY:

0.00739

AC XY:

5365

AN XY:

726020

show subpopulations

Gnomad4 AFR exome

AF:

0.000987

Gnomad4 AMR exome

AF:

0.00262

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00382

Gnomad4 FIN exome

AF:

0.00388

Gnomad4 NFE exome

AF:

0.00900

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00509

AC:

775

AN:

152302

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00928

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00685

Hom.:

Bravo

AF:

0.00459

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00796

EpiControl

AF:

0.00842

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PIP4P1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over