Variant rs343 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000237.3(LPL):c.430-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,316,296 control chromosomes in the GnomAD database, including 5,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 614 hom., cov: 33)

Exomes 𝑓: 0.090 ( 5058 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.510

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 8-19953276-C-A is Benign according to our data. Variant chr8-19953276-C-A is described in ClinVar as [Benign]. Clinvar id is 1230139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19953276-C-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3 linkuse as main transcript	c.430-34C>A		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1 linkuse as main transcript	c.430-34C>A		intron_variant			NM_000237.3	P1
LPL	ENST00000520959.5 linkuse as main transcript	c.202-34C>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0837

AC:

12729

AN:

152086

Hom.:

611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0515

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0676

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0824

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.0984

AC:

24640

AN:

250484

Hom.:

1363

AF XY:

0.0999

AC XY:

13533

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.128

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0649

Gnomad NFE exome

AF:

0.0813

Gnomad OTH exome

AF:

0.0987

GnomAD4 exome

AF:

0.0903

AC:

105163

AN:

1164092

Hom.:

5058

Cov.:

AF XY:

0.0924

AC XY:

54806

AN XY:

593430

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.137

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.0635

Gnomad4 NFE exome

AF:

0.0838

Gnomad4 OTH exome

AF:

0.0931

GnomAD4 genome

AF:

0.0837

AC:

12733

AN:

152204

Hom.:

614

Cov.:

AF XY:

0.0859

AC XY:

6392

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0514

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.155

Gnomad4 SAS

AF:

0.126

Gnomad4 FIN

AF:

0.0676

Gnomad4 NFE

AF:

0.0824

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.0912

Hom.:

690

Bravo

AF:

0.0861

Asia WGS

AF:

0.145

AC:

502

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.49

DANN

Benign

0.17

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over