rs3804264

Variant names:

• chr5-55447113-G-A
• rs3804264
• NM_003711.4:c.492-5205C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLPP1	NM_003711.4	c.492-5205C>T		intron_variant	Intron 3 of 5	ENST00000307259.9	NP_003702.2
PLPP1	NM_176895.3	c.495-5205C>T		intron_variant	Intron 3 of 5		NP_795714.1
PLPP1	NR_103485.2	n.982-5205C>T		intron_variant	Intron 4 of 6
PLPP1	XM_006714724.4	c.303-5205C>T		intron_variant	Intron 2 of 4		XP_006714787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPP1	ENST00000307259.9	c.492-5205C>T		intron_variant	Intron 3 of 5	1	NM_003711.4	ENSP00000302229.8

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

African (AFR) AF: 0.395 AC: 16379 AN: 41444

American (AMR) AF: 0.521 AC: 7966 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 2243 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2572 AN: 5162

South Asian (SAS) AF: 0.595 AC: 2868 AN: 4824

European-Finnish (FIN) AF: 0.496 AC: 5235 AN: 10552

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41623 AN: 67978

Other (OTH) AF: 0.532 AC: 1120 AN: 2106

Alfa AF: 0.586 Hom.: 16306

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
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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