rs4751996

Positions:

• chr10-116638383-A-G
• chr10-116638383-A-T

Variant summary

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

The ENST00000579578.6(PNLIPRP2):​c.1081A>G​(p.Ile361Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,259,318 control chromosomes in the GnomAD database, including 147,816 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict 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 (22965 hom., cov: 31)
  • Exomes 𝑓: 0.47 (124851 hom.)
• Consequence: PNLIPRP2 ENST00000579578.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4504615E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNLIPRP2	NR_103727.2	n.1107A>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.1081A>G	p.Ile361Val	missense_variant	11/13	2		ENSP00000463502	P1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82720 AN: 151614 Hom.: 22923 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.603

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: 0.481

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.528

GnomAD3 exomes AF: 0.492 AC: 82987 AN: 168656 Hom.: 21129 AF XY: 0.486 AC XY: 43148 AN XY: 88854

Gnomad AFR exome AF: 0.614

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.248

Gnomad SAS exome AF: 0.418

Gnomad FIN exome AF: 0.630

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.471 AC: 521727 AN: 1107586 Hom.: 124851 Cov.: 15 AF XY: 0.471 AC XY: 263591 AN XY: 559470

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.405

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.471

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.546 AC: 82827 AN: 151732 Hom.: 22965 Cov.: 31 AF XY: 0.548 AC XY: 40603 AN XY: 74146

Gnomad4 AFR AF: 0.621

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: 0.531

Alfa AF: 0.525 Hom.: 13311

Bravo AF: 0.543

TwinsUK AF: 0.530 AC: 1967

ALSPAC AF: 0.519 AC: 2000

ESP6500AA AF: 0.631 AC: 2316

ESP6500EA AF: 0.520 AC: 4248

ExAC AF: 0.427 AC: 47505

Asia WGS AF: 0.443 AC: 1539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	10
DANN	Benign	0.22
DEOGEN2	Benign	0.0018	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.000015	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.36	T
Vest4		0.060
ClinPred		0.027	T
GERP RS		2.6
Varity_R		0.030

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: rs4751996; hg19: chr10-118397894; COSMIC: COSV53945253; COSMIC: COSV53945253;