14-20460185-C-T

Variant names:

• chr14-20460185-C-T
• rs145530732
• NM_144568.4:c.440+7G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 3341540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144568.4. 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
	PIP4P1	NM_144568.4	MANE Select	c.440+7G>A		splice_region intron	N/A	NP_653169.2	Q86T03-1
	PIP4P1	NM_001100814.3		c.461+7G>A		splice_region intron	N/A	NP_001094284.1	Q86T03-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIP4P1	ENST00000250489.9	TSL:1 MANE Select	c.440+7G>A		splice_region intron	N/A	ENSP00000250489.4	Q86T03-1
	PIP4P1	ENST00000398020.6	TSL:1	c.461+7G>A		splice_region intron	N/A	ENSP00000381102.4	Q86T03-2
	PIP4P1	ENST00000924695.1		c.452+7G>A		splice_region intron	N/A	ENSP00000594754.1

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 774 AN: 152184 Hom.: 2 Cov.: 32

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

GnomAD2 exomes AF: 0.00513 AC: 1290 AN: 251472 AF XY: 0.00528

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 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.: 59 Cov.: 30 AF XY: 0.00739 AC XY: 5365 AN XY: 726020

African (AFR) AF: 0.000987 AC: 33 AN: 33420

American (AMR) AF: 0.00262 AC: 117 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.00382 AC: 329 AN: 86190

European-Finnish (FIN) AF: 0.00388 AC: 207 AN: 53414

Middle Eastern (MID) AF: 0.00261 AC: 15 AN: 5752

European-Non Finnish (NFE) AF: 0.00900 AC: 9981 AN: 1109274

Other (OTH) AF: 0.00614 AC: 370 AN: 60278

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00443 AC XY: 330 AN XY: 74476

African (AFR) AF: 0.00106 AC: 44 AN: 41556

American (AMR) AF: 0.00209 AC: 32 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4832

European-Finnish (FIN) AF: 0.00349 AC: 37 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00928 AC: 631 AN: 68018

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00685 Hom.: 2

Bravo AF: 0.00459

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00796

EpiControl AF: 0.00842

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		1.4
PromoterAI		0.00020	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs145530732; hg19: chr14-20928344;