Genetic Variant LPL:c.430-34C>T (chr8-19953276-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is . The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000237.3(LPL):c.430-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000858 in 1,164,960 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.510

Publications

0 publications found

Variant links:

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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Genomics England PanelApp, Ambry Genetics
hyperlipidemia, familial combined, LPL related
Inheritance: SD, AD Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp

LPL links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000237.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.430-34C>T		intron	N/A	NP_000228.1	P06858

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPL	ENST00000650287.1	MANE Select	c.430-34C>T	intron	N/A	ENSP00000497642.1	P06858
LPL	ENST00000965928.1		c.430-34C>T	intron	N/A	ENSP00000635987.1
LPL	ENST00000965929.1		c.430-37C>T	intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.58e-7

AC:

AN:

1164960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

593826

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27818

American (AMR)

AF:

0.00

AC:

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24296

East Asian (EAS)

AF:

0.00

AC:

AN:

38248

South Asian (SAS)

AF:

0.00

AC:

AN:

80440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5206

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

841288

Other (OTH)

AF:

0.00

AC:

AN:

50288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.52

(source)

DANN

Benign

0.16

PhyloP100

-0.51

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over