15-58509744-A-G

Variant names:

• chr15-58509744-A-G
• rs4775065
• NM_000236.3:c.89-28589A>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.89-28589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,906 control chromosomes in the GnomAD database, including 38,362 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 0.71 (38362 hom., cov: 30)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.89-28589A>G		intron_variant	Intron 1 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.89-28589A>G		intron_variant	Intron 1 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107535 AN: 151788 Hom.: 38331 Cov.: 30

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.708 AC: 107619 AN: 151906 Hom.: 38362 Cov.: 30 AF XY: 0.703 AC XY: 52175 AN XY: 74220

African (AFR) AF: 0.626 AC: 25939 AN: 41426

American (AMR) AF: 0.717 AC: 10936 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2400 AN: 3462

East Asian (EAS) AF: 0.745 AC: 3825 AN: 5136

South Asian (SAS) AF: 0.595 AC: 2864 AN: 4810

European-Finnish (FIN) AF: 0.684 AC: 7216 AN: 10546

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 51993 AN: 67972

Other (OTH) AF: 0.715 AC: 1502 AN: 2102

Alfa AF: 0.745 Hom.: 60731

Bravo AF: 0.711

Asia WGS AF: 0.700 AC: 2434 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		0.61
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: rs4775065; hg19: chr15-58801943;