rs252

Variant names:

• chr8-19953720-TA-T
• rs252
• NM_000237.3:c.541+302delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000237.3(LPL):​c.541+302delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (25756 hom., cov: 0)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 7 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 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.541+302delA		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.541+300delA		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.541+300delA		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.538+300delA		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 84064 AN: 151886 Hom.: 25705 Cov.: 0

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.554 AC: 84162 AN: 152004 Hom.: 25756 Cov.: 0 AF XY: 0.547 AC XY: 40653 AN XY: 74270

African (AFR) AF: 0.831 AC: 34483 AN: 41496

American (AMR) AF: 0.469 AC: 7157 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1414 AN: 3466

East Asian (EAS) AF: 0.346 AC: 1780 AN: 5146

South Asian (SAS) AF: 0.406 AC: 1958 AN: 4820

European-Finnish (FIN) AF: 0.450 AC: 4746 AN: 10544

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31048 AN: 67948

Other (OTH) AF: 0.491 AC: 1033 AN: 2104

Alfa AF: 0.517 Hom.: 2667

Bravo AF: 0.562

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

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: rs252; hg19: chr8-19811231;