Genetic Variant LIPC:c.88+43435C>G (chr15-58475555-C-G) – 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.88+43435C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 151,974 control chromosomes in the GnomAD database, including 16,644 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 0.47 ( 16644 hom., cov: 32)

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.972

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:

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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 = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.88+43435C>G		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2	P11150A6H8L5
LIPC-AS1	NR_120338.1 link	n.208+19218G>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10 link	c.88+43435C>G		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5		P11150

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71036

AN:

151854

Hom.:

16622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.518

Gnomad ASJ

AF:

0.428

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.459

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

GnomAD4 genome

AF:

0.468

AC:

71094

AN:

151974

Hom.:

16644

Cov.:

AF XY:

0.462

AC XY:

34302

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.437

AC:

18089

AN:

41392

American (AMR)

AF:

0.519

AC:

7927

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.428

AC:

1486

AN:

3472

East Asian (EAS)

AF:

0.437

AC:

2255

AN:

5160

South Asian (SAS)

AF:

0.366

AC:

1762

AN:

4820

European-Finnish (FIN)

AF:

0.408

AC:

4322

AN:

10588

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.495

AC:

33609

AN:

67946

Other (OTH)

AF:

0.454

AC:

957

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1934

3868

5803

7737

9671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.358

Hom.:

941

Bravo

AF:

0.478

Asia WGS

AF:

0.383

AC:

1335

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

(source)

DANN

Benign

0.63

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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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15-58475555-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over