rs3804264

Positions:

• chr5-55447113-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003711.4(PLPP1):​c.492-5205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,024 control chromosomes in the GnomAD database, including 22,126 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 0.53 (22126 hom., cov: 33)
• Consequence: PLPP1 NM_003711.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.159

Genes affected

PLPP1 (HGNC:9228): (phospholipid phosphatase 1) The protein encoded by this gene is a member of the phosphatidic acid phosphatase (PAP) family. PAPs convert phosphatidic acid to diacylglycerol, and function in synthesis of glycerolipids and in phospholipase D-mediated signal transduction. This enzyme is an integral membrane glycoprotein that plays a role in the hydrolysis and uptake of lipids from extracellular space. Alternate splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLPP1	NM_003711.4	c.492-5205C>T		intron_variant		ENST00000307259.9	NP_003702.2
PLPP1	NM_176895.3	c.495-5205C>T		intron_variant			NP_795714.1
PLPP1	XM_006714724.4	c.303-5205C>T		intron_variant			XP_006714787.1
PLPP1	NR_103485.2	n.982-5205C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPP1	ENST00000307259.9	c.492-5205C>T		intron_variant		1	NM_003711.4	ENSP00000302229	P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80728 AN: 151906 Hom.: 22126 Cov.: 33

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.531 AC: 80754 AN: 152024 Hom.: 22126 Cov.: 33 AF XY: 0.526 AC XY: 39103 AN XY: 74294

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.532

Alfa AF: 0.592 Hom.: 10823

Bravo AF: 0.525

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs3804264; hg19: chr5-54742941; COSMIC: COSV53307921;