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.*1250A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,200 control chromosomes in the GnomAD database, including 3,247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3247 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LPL
NM_000237.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.643

Publications

31 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=-0.79).

BP6

Variant 8-19966560-A-G is Benign according to our data. Variant chr8-19966560-A-G is described in ClinVar as Benign. ClinVar VariationId is 362441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.*1250A>G		3_prime_UTR	Exon 10 of 10	NP_000228.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LPL	ENST00000650287.1	MANE Select	c.*1250A>G	3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
LPL	ENST00000650478.1		n.*1501A>G	non_coding_transcript_exon	Exon 4 of 4	ENSP00000497560.1
LPL	ENST00000650478.1		n.*1501A>G	3_prime_UTR	Exon 4 of 4	ENSP00000497560.1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29529

AN:

152080

Hom.:

3251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.182

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.194

AC:

29527

AN:

152200

Hom.:

3247

Cov.:

AF XY:

0.194

AC XY:

14430

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.118

AC:

4903

AN:

41546

American (AMR)

AF:

0.184

AC:

2805

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

416

AN:

3468

East Asian (EAS)

AF:

0.130

AC:

676

AN:

5188

South Asian (SAS)

AF:

0.146

AC:

702

AN:

4820

European-Finnish (FIN)

AF:

0.305

AC:

3219

AN:

10568

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16144

AN:

68004

Other (OTH)

AF:

0.180

AC:

381

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1202

2403

3605

4806

6008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.220

Hom.:

2035

Bravo

AF:

0.184

Asia WGS

AF:

0.112

AC:

392

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hyperlipoproteinemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.2

(source)

DANN

Benign

0.70

PhyloP100

0.64

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over