1-98987731-T-C

Position:

• chr1-98987731-T-C

Variant summary

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

The NM_001037317.2(PLPPR5):​c.237+16704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,694 control chromosomes in the GnomAD database, including 7,960 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 0.30 (7960 hom., cov: 32)
• Consequence: PLPPR5 NM_001037317.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

Genes affected

PLPPR5 (HGNC:31703): (phospholipid phosphatase related 5) The protein encoded by this gene is a type 2 member of the phosphatidic acid phosphatase (PAP) family. All type 2 members of this protein family contain 6 transmembrane regions, and a consensus N-glycosylation site. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLPPR5	NM_001037317.2	c.237+16704A>G		intron_variant		ENST00000263177.5
PLPPR5	NM_001010861.3	c.237+16704A>G		intron_variant
PLPPR5	XM_011540838.4	c.189+16704A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR5	ENST00000263177.5	c.237+16704A>G		intron_variant		1	NM_001037317.2	P4
PLPPR5	ENST00000370188.7	c.237+16704A>G		intron_variant		1		A1
PLPPR5	ENST00000672681.1	c.237+16704A>G		intron_variant
PLPPR5	ENST00000696571.1	c.73-30990A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45129 AN: 151576 Hom.: 7962 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0349

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.298 AC: 45130 AN: 151694 Hom.: 7960 Cov.: 32 AF XY: 0.294 AC XY: 21771 AN XY: 74082

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.291

Alfa AF: 0.366 Hom.: 13481

Bravo AF: 0.289

Asia WGS AF: 0.143 AC: 500 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.8
DANN	Benign	0.84

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: rs10443196; hg19: chr1-99453287;