rs283

Variant names:

• chr8-19957587-C-T
• rs283
• NM_000237.3:c.1018+1504C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000237.3(LPL):​c.1018+1504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,048 control chromosomes in the GnomAD database, including 7,126 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 0.28 (7126 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839
• Publications: 31 publications found

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1018+1504C>T		intron_variant	Intron 6 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1018+1504C>T		intron_variant	Intron 6 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.79+1504C>T		intron_variant	Intron 1 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42626 AN: 151930 Hom.: 7100 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.281 AC: 42701 AN: 152048 Hom.: 7126 Cov.: 32 AF XY: 0.278 AC XY: 20651 AN XY: 74322

African (AFR) AF: 0.473 AC: 19595 AN: 41436

American (AMR) AF: 0.236 AC: 3606 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3472

East Asian (EAS) AF: 0.126 AC: 654 AN: 5170

South Asian (SAS) AF: 0.167 AC: 804 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2708 AN: 10550

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13888 AN: 67992

Other (OTH) AF: 0.261 AC: 550 AN: 2110

Alfa AF: 0.231 Hom.: 910

Bravo AF: 0.290

Asia WGS AF: 0.155 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.76
PhyloP100		-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

Other links and lift over

dbSNP: rs283; hg19: chr8-19815098;