NM_000237.3:c.1019-1582C>T

Variant names:

• chr8-19957678-C-T
• rs285
• NM_000237.3:c.1019-1582C>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.1019-1582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,044 control chromosomes in the GnomAD database, including 28,584 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 0.58 (28584 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 67 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.1019-1582C>T		intron	N/A	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.1019-1582C>T		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.1019-1582C>T		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.1016-1582C>T		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88429 AN: 151926 Hom.: 28528 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.582 AC: 88535 AN: 152044 Hom.: 28584 Cov.: 32 AF XY: 0.575 AC XY: 42746 AN XY: 74310

African (AFR) AF: 0.877 AC: 36397 AN: 41502

American (AMR) AF: 0.490 AC: 7487 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1560 AN: 3468

East Asian (EAS) AF: 0.332 AC: 1707 AN: 5148

South Asian (SAS) AF: 0.397 AC: 1916 AN: 4822

European-Finnish (FIN) AF: 0.503 AC: 5304 AN: 10548

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32485 AN: 67968

Other (OTH) AF: 0.527 AC: 1109 AN: 2106

Alfa AF: 0.519 Hom.: 40999

Bravo AF: 0.591

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.24
PhyloP100		0.13

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: rs285; hg19: chr8-19815189;