Genetic Variant NM_000236.3:c.88+22511T>C (chr15-58454631-T-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.88+22511T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,078 control chromosomes in the GnomAD database, including 10,043 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 0.36 ( 10039 hom., cov: 33)

Exomes 𝑓: 0.42 ( 4 hom. )

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41

Publications

20 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:

ENSG00000277229 (HGNC:):

ENSG00000277229 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.88+22511T>C		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2
LIPC-AS1	NR_120338.1 link	n.209-17719A>G		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+22511T>C		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54621

AN:

151912

Hom.:

10026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.489

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.375

GnomAD4 exome

AF:

0.417

AC:

AN:

Hom.:

Cov.:

AF XY:

0.450

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.412

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.360

AC:

54670

AN:

152030

Hom.:

10039

Cov.:

AF XY:

0.361

AC XY:

26800

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.382

AC:

15834

AN:

41464

American (AMR)

AF:

0.452

AC:

6912

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1436

AN:

3470

East Asian (EAS)

AF:

0.490

AC:

2521

AN:

5148

South Asian (SAS)

AF:

0.397

AC:

1914

AN:

4824

European-Finnish (FIN)

AF:

0.281

AC:

2967

AN:

10570

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21878

AN:

67964

Other (OTH)

AF:

0.371

AC:

783

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1831

3662

5494

7325

9156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.347

Hom.:

33961

Bravo

AF:

0.376

Asia WGS

AF:

0.408

AC:

1425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

(source)

DANN

Benign

0.73

PhyloP100

1.4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over