dbSNP rs12593880: LIPC:c.89-50891C>A (chr15-58487442-C-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.89-50891C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,262 control chromosomes in the GnomAD database, including 734 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 0.088 ( 734 hom., cov: 33)

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.658

Publications

9 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 links:

ALDH1A2 (HGNC:15472): (aldehyde dehydrogenase 1 family member A2) This protein belongs to the aldehyde dehydrogenase family of proteins. The product of this gene is an enzyme that catalyzes the synthesis of retinoic acid (RA) from retinaldehyde. Retinoic acid, the active derivative of vitamin A (retinol), is a hormonal signaling molecule that functions in developing and adult tissues. The studies of a similar mouse gene suggest that this enzyme and the cytochrome CYP26A1, concurrently establish local embryonic retinoic acid levels which facilitate posterior organ development and prevent spina bifida. Four transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, May 2011]

ALDH1A2 links:

LIPC-AS1 (HGNC:52294): (LIPC antisense RNA 1)

LIPC-AS1 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=-0.75).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.89-50891C>A		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2	P11150A6H8L5
LIPC-AS1	NR_120338.1 link	n.208+7331G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10 link	c.89-50891C>A		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5		P11150

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13443

AN:

152144

Hom.:

734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.0617

Gnomad EAS

AF:

0.0849

Gnomad SAS

AF:

0.0548

Gnomad FIN

AF:

0.0961

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.0750

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0882

AC:

13435

AN:

152262

Hom.:

734

Cov.:

AF XY:

0.0853

AC XY:

6352

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0237

AC:

984

AN:

41554

American (AMR)

AF:

0.0885

AC:

1354

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0617

AC:

214

AN:

3470

East Asian (EAS)

AF:

0.0847

AC:

438

AN:

5172

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4830

European-Finnish (FIN)

AF:

0.0961

AC:

1020

AN:

10614

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8809

AN:

68000

Other (OTH)

AF:

0.0742

AC:

157

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

630

1259

1889

2518

3148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.114

Hom.:

1946

Bravo

AF:

0.0855

Asia WGS

AF:

0.0760

AC:

263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.4

(source)

DANN

Benign

0.84

PhyloP100

-0.66

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over