dbSNP rs301: LPL:c.1139+43T>C (chr8-19959423-T-C) – ACMG Classification: Benign (-20 pts)

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.1139+43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,607,608 control chromosomes in the GnomAD database, including 45,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4970 hom., cov: 31)

Exomes 𝑓: 0.24 ( 40525 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.14

Publications

74 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=-0.95).

BP6

Variant 8-19959423-T-C is Benign according to our data. Variant chr8-19959423-T-C is described in ClinVar as Benign. ClinVar VariationId is 1278475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3 link	c.1139+43T>C		intron_variant	Intron 7 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.1139+43T>C		intron_variant	Intron 7 of 9		NM_000237.3	ENSP00000497642.1		P06858
LPL	ENST00000650478.1 link	n.80-1478T>C		intron_variant	Intron 1 of 3			ENSP00000497560.1		A0A3B3IT60

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38561

AN:

151894

Hom.:

4962

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.306

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.238

GnomAD2 exomes

AF:

0.242

AC:

58705

AN:

242970

AF XY:

0.240

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.236

GnomAD4 exome

AF:

0.235

AC:

342332

AN:

1455596

Hom.:

40525

Cov.:

AF XY:

0.235

AC XY:

170364

AN XY:

723906

show subpopulations

African (AFR)

AF:

0.303

AC:

10124

AN:

33394

American (AMR)

AF:

0.201

AC:

8793

AN:

43814

Ashkenazi Jewish (ASJ)

AF:

0.318

AC:

8262

AN:

26014

East Asian (EAS)

AF:

0.202

AC:

7971

AN:

39444

South Asian (SAS)

AF:

0.224

AC:

19244

AN:

85992

European-Finnish (FIN)

AF:

0.235

AC:

12233

AN:

52160

Middle Eastern (MID)

AF:

0.229

AC:

1305

AN:

5696

European-Non Finnish (NFE)

AF:

0.235

AC:

260115

AN:

1108978

Other (OTH)

AF:

0.238

AC:

14285

AN:

60104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

12057

24114

36172

48229

60286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8996

17992

26988

35984

44980

<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:

0.254

AC:

38583

AN:

152012

Hom.:

4970

Cov.:

AF XY:

0.252

AC XY:

18700

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.302

AC:

12505

AN:

41440

American (AMR)

AF:

0.226

AC:

3449

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1061

AN:

3470

East Asian (EAS)

AF:

0.206

AC:

1060

AN:

5154

South Asian (SAS)

AF:

0.221

AC:

1067

AN:

4822

European-Finnish (FIN)

AF:

0.221

AC:

2341

AN:

10574

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16239

AN:

67986

Other (OTH)

AF:

0.239

AC:

504

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1463

2927

4390

5854

7317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<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:

0.244

Hom.:

15018

Bravo

AF:

0.254

Asia WGS

AF:

0.232

AC:

804

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.081

(source)

DANN

Benign

0.46

PhyloP100

-4.1

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

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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