Genetic Variant NM_000236.3:c.89-16966A>C (chr15-58521367-A-C) – 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.89-16966A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,116 control chromosomes in the GnomAD database, including 35,069 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 0.65 ( 35001 hom., cov: 30)

Exomes 𝑓: 0.76 ( 68 hom. )

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.145

Publications

1 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.771 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.89-16966A>C		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.89-16966A>C	intron	N/A	ENSP00000299022.5	P11150
LIPC	ENST00000414170.7	TSL:1	c.89-16966A>C	intron	N/A	ENSP00000395569.3	E7EUJ1
ENSG00000259476	ENST00000561202.1	TSL:1	n.57A>C	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99245

AN:

151778

Hom.:

34996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.814

Gnomad AMR

AF:

0.769

Gnomad ASJ

AF:

0.741

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.725

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.718

GnomAD4 exome

AF:

0.764

AC:

168

AN:

220

Hom.:

Cov.:

AF XY:

0.756

AC XY:

130

AN XY:

172

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.755

AC:

148

AN:

196

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.544

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.654

AC:

99265

AN:

151896

Hom.:

35001

Cov.:

AF XY:

0.656

AC XY:

48687

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.359

AC:

14842

AN:

41350

American (AMR)

AF:

0.770

AC:

11749

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.741

AC:

2574

AN:

3472

East Asian (EAS)

AF:

0.729

AC:

3749

AN:

5140

South Asian (SAS)

AF:

0.725

AC:

3495

AN:

4824

European-Finnish (FIN)

AF:

0.716

AC:

7553

AN:

10546

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.777

AC:

52823

AN:

67988

Other (OTH)

AF:

0.719

AC:

1514

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1480

2960

4440

5920

7400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.657

Hom.:

3439

Bravo

AF:

0.648

Asia WGS

AF:

0.712

AC:

2473

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.0

(source)

DANN

Benign

0.52

PhyloP100

-0.14

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over