15-58547840-A-G

Variant names:

• chr15-58547840-A-G
• rs7165654
• NM_000236.3:c.809-490A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.809-490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,830 control chromosomes in the GnomAD database, including 37,565 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 0.70 (37565 hom., cov: 29)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 5 publications found

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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.809-490A>G		intron_variant	Intron 5 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.809-490A>G		intron_variant	Intron 5 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105579 AN: 151712 Hom.: 37560 Cov.: 29

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.738

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

GnomAD4 genome AF: 0.696 AC: 105608 AN: 151830 Hom.: 37565 Cov.: 29 AF XY: 0.689 AC XY: 51067 AN XY: 74162

African (AFR) AF: 0.595 AC: 24615 AN: 41350

American (AMR) AF: 0.730 AC: 11150 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2749 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2051 AN: 5148

South Asian (SAS) AF: 0.585 AC: 2805 AN: 4796

European-Finnish (FIN) AF: 0.645 AC: 6794 AN: 10528

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.778 AC: 52839 AN: 67954

Other (OTH) AF: 0.738 AC: 1555 AN: 2106

Alfa AF: 0.744 Hom.: 19831

Bravo AF: 0.696

Asia WGS AF: 0.482 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.10
DANN	Benign	0.28
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7165654; hg19: chr15-58840039;