Variant chr8-19954390-T-C 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.775+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,581,682 control chromosomes in the GnomAD database, including 20,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2545 hom., cov: 33)

Exomes 𝑓: 0.16 ( 17824 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0960

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=-0.83).

BP6

Variant 8-19954390-T-C is Benign according to our data. Variant chr8-19954390-T-C is described in ClinVar as [Benign]. Clinvar id is 1182670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19954390-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3 link	c.775+37T>C		intron_variant		ENST00000650287.1	NP_000228.1	P06858A0A1B1RVA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1 link	c.775+37T>C		intron_variant			NM_000237.3	ENSP00000497642.1		P06858

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26799

AN:

152036

Hom.:

2533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.190

Gnomad EAS

AF:

0.223

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.167

AC:

41243

AN:

247204

Hom.:

3574

AF XY:

0.168

AC XY:

22481

AN XY:

133784

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.224

Gnomad SAS exome

AF:

0.222

Gnomad FIN exome

AF:

0.102

Gnomad NFE exome

AF:

0.146

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.155

AC:

221787

AN:

1429528

Hom.:

17824

Cov.:

AF XY:

0.157

AC XY:

112071

AN XY:

713296

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.217

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.105

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.176

AC:

26835

AN:

152154

Hom.:

2545

Cov.:

AF XY:

0.176

AC XY:

13104

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.174

Gnomad4 ASJ

AF:

0.190

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.224

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.168

Hom.:

719

Bravo

AF:

0.181

Asia WGS

AF:

0.234

AC:

813

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	Apr 01, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.8

DANN

Benign

0.27

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