rs12769643

Positions:

• chr10-120510614-G-A
• chr10-120510614-G-C
• chr10-120510614-G-T

Variant summary

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

The NM_001030059.3(PLPP4):​c.166-3297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,938 control chromosomes in the GnomAD database, including 13,906 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 0.43 (13906 hom., cov: 32)
• Consequence: PLPP4 NM_001030059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

PLPP4 (HGNC:23531): (phospholipid phosphatase 4) Enables diacylglycerol diphosphate phosphatase activity; identical protein binding activity; and phosphatidate phosphatase activity. Involved in phospholipid dephosphorylation and regulation of calcium ion import. Predicted to be located in plasma membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPP4	NM_001030059.3	c.166-3297G>A		intron_variant		ENST00000398250.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPP4	ENST00000398250.6	c.166-3297G>A		intron_variant		1	NM_001030059.3	P1
PLPP4	ENST00000369073.3	n.136-3297G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64717 AN: 151820 Hom.: 13894 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.426 AC: 64778 AN: 151938 Hom.: 13906 Cov.: 32 AF XY: 0.426 AC XY: 31610 AN XY: 74252

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.436

Alfa AF: 0.432 Hom.: 13562

Bravo AF: 0.426

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.075
DANN	Benign	0.71

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: rs12769643; hg19: chr10-122270126;