dbSNP rs11856322: LIPC:c.89-50519G>A (chr15-58487814-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.89-50519G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,098 control chromosomes in the GnomAD database, including 5,301 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 0.26 ( 5301 hom., cov: 32)

Consequence

LIPC
NM_000236.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

Publications

3 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3 link	c.89-50519G>A		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2	P11150A6H8L5
LIPC-AS1	NR_120338.1 link	n.208+6959C>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.89-50519G>A		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5		P11150

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39977

AN:

151980

Hom.:

5294

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.269

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

GnomAD4 genome

AF:

0.263

AC:

39993

AN:

152098

Hom.:

5301

Cov.:

AF XY:

0.269

AC XY:

20001

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.213

AC:

8840

AN:

41498

American (AMR)

AF:

0.240

AC:

3675

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

847

AN:

3470

East Asian (EAS)

AF:

0.322

AC:

1660

AN:

5152

South Asian (SAS)

AF:

0.303

AC:

1462

AN:

4824

European-Finnish (FIN)

AF:

0.391

AC:

4127

AN:

10550

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.273

AC:

18580

AN:

67996

Other (OTH)

AF:

0.276

AC:

583

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1554

3109

4663

6218

7772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.269

Hom.:

21558

Bravo

AF:

0.251

Asia WGS

AF:

0.361

AC:

1253

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

9.1

(source)

DANN

Benign

0.32

PhyloP100

0.63

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