rs316

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000237.3(LPL):c.1164C>A(p.Thr388Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,612,340 control chromosomes in the GnomAD database, including 14,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2009 hom., cov: 31)

Exomes 𝑓: 0.13 ( 12298 hom. )

Consequence

LPL
NM_000237.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.57

Publications

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

LPL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 8-19960925-C-A is Benign according to our data. Variant chr8-19960925-C-A is described in ClinVar as Benign. ClinVar VariationId is 362413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3 link	c.1164C>A	p.Thr388Thr	synonymous_variant	Exon 8 of 10	ENST00000650287.1	NP_000228.1	P06858A0A1B1RVA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1 link	c.1164C>A	p.Thr388Thr	synonymous_variant	Exon 8 of 10		NM_000237.3	ENSP00000497642.1		P06858
LPL	ENST00000650478.1 link	n.104C>A		non_coding_transcript_exon_variant	Exon 2 of 4			ENSP00000497560.1		A0A3B3IT60

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23541

AN:

151804

Hom.:

2000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.110

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.143

GnomAD2 exomes

AF:

0.135

AC:

33843

AN:

251348

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.0965

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.127

AC:

185694

AN:

1460422

Hom.:

12298

Cov.:

AF XY:

0.127

AC XY:

92390

AN XY:

726602

show subpopulations

African (AFR)

AF:

0.226

AC:

7539

AN:

33432

American (AMR)

AF:

0.133

AC:

5943

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5481

AN:

26106

East Asian (EAS)

AF:

0.0777

AC:

3084

AN:

39684

South Asian (SAS)

AF:

0.127

AC:

10988

AN:

86224

European-Finnish (FIN)

AF:

0.134

AC:

7166

AN:

53396

Middle Eastern (MID)

AF:

0.125

AC:

712

AN:

5712

European-Non Finnish (NFE)

AF:

0.123

AC:

136657

AN:

1110800

Other (OTH)

AF:

0.135

AC:

8124

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

8366

16732

25099

33465

41831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5064

10128

15192

20256

25320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23575

AN:

151918

Hom.:

2009

Cov.:

AF XY:

0.154

AC XY:

11435

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.223

AC:

9225

AN:

41416

American (AMR)

AF:

0.141

AC:

2152

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

696

AN:

3472

East Asian (EAS)

AF:

0.0964

AC:

494

AN:

5126

South Asian (SAS)

AF:

0.122

AC:

587

AN:

4810

European-Finnish (FIN)

AF:

0.130

AC:

1367

AN:

10546

Middle Eastern (MID)

AF:

0.115

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.127

AC:

8604

AN:

67956

Other (OTH)

AF:

0.144

AC:

305

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

964

1929

2893

3858

4822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

4443

Bravo

AF:

0.157

Asia WGS

AF:

0.128

AC:

442

AN:

3478

EpiCase

AF:

0.122

EpiControl

AF:

0.121

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hyperlipoproteinemia, type I

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 20, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Dec 03, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.4

(source)

DANN

Benign

0.35

PhyloP100

-2.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over