rs4751995

Positions:

• chr10-116638373-A-G
• chr10-116638373-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The ENST00000579578.6(PNLIPRP2):​c.1071A>G​(p.Ter357TrpextTer?) variant causes a stop lost change. The variant allele was found at a frequency of 0.468 in 1,113,658 control chromosomes in the GnomAD database, including 124,765 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 0.55 (23011 hom., cov: 31)
  • Exomes 𝑓: 0.46 (101754 hom.)
• Consequence: PNLIPRP2 ENST00000579578.6 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

Genes affected

PNLIPRP2 (HGNC:9157): (pancreatic lipase related protein 2 (gene/pseudogene)) This gene encodes a lipase that hydrolyzes galactolipids, the main components of plant membrane lipids. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the non-coding allele. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in ENST00000579578.6 Downstream stopcodon found after 364 codons.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNLIPRP2	NR_103727.2	n.1097A>G		non_coding_transcript_exon_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNLIPRP2	ENST00000579578.6	c.1071A>G	p.Ter357TrpextTer?	stop_lost	11/13	2		ENSP00000463502	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82791 AN: 151630 Hom.: 22966 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.529

GnomAD3 exomes AF: 0.492 AC: 77564 AN: 157686 Hom.: 19779 AF XY: 0.486 AC XY: 40285 AN XY: 82966

Gnomad AFR exome AF: 0.612

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.499

Gnomad EAS exome AF: 0.245

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.495

GnomAD4 exome AF: 0.456 AC: 438756 AN: 961910 Hom.: 101754 Cov.: 13 AF XY: 0.457 AC XY: 224958 AN XY: 492074

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.494

Gnomad4 ASJ exome AF: 0.489

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.401

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.469

GnomAD4 genome AF: 0.546 AC: 82901 AN: 151748 Hom.: 23011 Cov.: 31 AF XY: 0.548 AC XY: 40638 AN XY: 74152

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.532

Alfa AF: 0.518 Hom.: 27956

Bravo AF: 0.544

TwinsUK AF: 0.530 AC: 1967

ALSPAC AF: 0.519 AC: 2000

ESP6500AA AF: 0.632 AC: 2314

ESP6500EA AF: 0.518 AC: 4225

ExAC AF: 0.430 AC: 47563

Asia WGS AF: 0.445 AC: 1546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.70
FATHMM_MKL	Benign	0.018	N
MutationTaster	Benign	1.5e-28	P
GERP RS		5.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4751995; hg19: chr10-118397884; COSMIC: COSV53945236; COSMIC: COSV53945236;