8-19965299-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000237.3(LPL):c.1428-11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 780,010 control chromosomes in the GnomAD database, including 4,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 660 hom., cov: 32)

Exomes 𝑓: 0.10 ( 3394 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Splicing: ADA: 0.00003292

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.151

Publications

28 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 -20 ACMG points.

BP4

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

BP6

Variant 8-19965299-C-T is Benign according to our data. Variant chr8-19965299-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3 link	c.1428-11C>T		intron_variant	Intron 9 of 9	ENST00000650287.1	NP_000228.1	P06858A0A1B1RVA9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1 link	c.1428-11C>T		intron_variant	Intron 9 of 9		NM_000237.3	ENSP00000497642.1		P06858
LPL	ENST00000650478.1 link	n.*251-11C>T		intron_variant	Intron 3 of 3			ENSP00000497560.1		A0A3B3IT60

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14328

AN:

152036

Hom.:

661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0716

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.0836

Gnomad ASJ

AF:

0.109

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0967

Gnomad FIN

AF:

0.0921

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0934

GnomAD2 exomes

AF:

0.0954

AC:

23944

AN:

250918

AF XY:

0.0971

show subpopulations

Gnomad AFR exome

AF:

0.0721

Gnomad AMR exome

AF:

0.0583

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0893

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0998

GnomAD4 exome

AF:

0.0999

AC:

62700

AN:

627856

Hom.:

3394

Cov.:

AF XY:

0.101

AC XY:

34510

AN XY:

342038

show subpopulations

African (AFR)

AF:

0.0714

AC:

1261

AN:

17666

American (AMR)

AF:

0.0611

AC:

2665

AN:

43624

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2309

AN:

20936

East Asian (EAS)

AF:

0.123

AC:

4424

AN:

36032

South Asian (SAS)

AF:

0.0938

AC:

6532

AN:

69642

European-Finnish (FIN)

AF:

0.0905

AC:

4805

AN:

53078

Middle Eastern (MID)

AF:

0.0975

AC:

404

AN:

4144

European-Non Finnish (NFE)

AF:

0.106

AC:

37161

AN:

349680

Other (OTH)

AF:

0.0950

AC:

3139

AN:

33054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

2554

5107

7661

10214

12768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.0941

AC:

14316

AN:

152154

Hom.:

660

Cov.:

AF XY:

0.0933

AC XY:

6937

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.0714

AC:

2964

AN:

41524

American (AMR)

AF:

0.0836

AC:

1278

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.109

AC:

380

AN:

3472

East Asian (EAS)

AF:

0.109

AC:

561

AN:

5168

South Asian (SAS)

AF:

0.0964

AC:

464

AN:

4814

European-Finnish (FIN)

AF:

0.0921

AC:

976

AN:

10592

Middle Eastern (MID)

AF:

0.103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.108

AC:

7327

AN:

67980

Other (OTH)

AF:

0.0924

AC:

195

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

677

1354

2032

2709

3386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.103

Hom.:

1147

Bravo

AF:

0.0920

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 10, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 03, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.3

(source)

DANN

Benign

0.72

PhyloP100

-0.15

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000033

dbscSNV1_RF

Benign

0.0

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

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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