dbSNP rs11071386: LIPC:c.89-15212G>A (chr15-58523121-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000236.3(LIPC):c.89-15212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,180 control chromosomes in the GnomAD database, including 24,927 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 24902 hom., cov: 32)

Exomes 𝑓: 0.68 ( 25 hom. )

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

11 publications found

Variant links:

Genes affected

LIPC (HGNC:6619): (lipase C, hepatic type) Enables phospholipase A1 activity and triglyceride lipase activity. Involved in several processes, including lipid homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer's disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus. [provided by Alliance of Genome Resources, Apr 2022]

LIPC Gene-Disease associations (from GenCC):

hyperlipidemia due to hepatic triglyceride lipase deficiency
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

LIPC links:

ENSG00000259476 (HGNC:):

ENSG00000259476 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.89-15212G>A		intron	N/A	NP_000227.2	P11150

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIPC	ENST00000299022.10	TSL:1 MANE Select	c.89-15212G>A	intron	N/A	ENSP00000299022.5	P11150
LIPC	ENST00000414170.7	TSL:1	c.89-15212G>A	intron	N/A	ENSP00000395569.3	E7EUJ1
ENSG00000259476	ENST00000561202.1	TSL:1	n.1507G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84005

AN:

151956

Hom.:

24885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.684

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.608

GnomAD4 exome

AF:

0.679

AC:

AN:

106

Hom.:

Cov.:

AF XY:

0.741

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.688

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.667

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.553

AC:

84032

AN:

152074

Hom.:

24902

Cov.:

AF XY:

0.557

AC XY:

41405

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.315

AC:

13054

AN:

41482

American (AMR)

AF:

0.684

AC:

10462

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.581

AC:

2017

AN:

3470

East Asian (EAS)

AF:

0.603

AC:

3106

AN:

5154

South Asian (SAS)

AF:

0.624

AC:

2997

AN:

4802

European-Finnish (FIN)

AF:

0.629

AC:

6661

AN:

10582

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43671

AN:

67980

Other (OTH)

AF:

0.611

AC:

1289

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1777

3553

5330

7106

8883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.624

Hom.:

55962

Bravo

AF:

0.547

Asia WGS

AF:

0.593

AC:

2061

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.73

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Computational scores

Splicing

Publications

Other links and lift over