15-58544109-C-T

Variant names:

• chr15-58544109-C-T
• rs11852861
• NM_000236.3:c.574+1458C>T

Variant summary

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

The NM_000236.3(LIPC):​c.574+1458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,096 control chromosomes in the GnomAD database, including 8,644 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 0.31 (8644 hom., cov: 32)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.574+1458C>T		intron	N/A	NP_000227.2	P11150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.574+1458C>T		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.574+1458C>T		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.431+1458C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46531 AN: 151978 Hom.: 8645 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.306 AC: 46531 AN: 152096 Hom.: 8644 Cov.: 32 AF XY: 0.303 AC XY: 22542 AN XY: 74328

African (AFR) AF: 0.109 AC: 4513 AN: 41512

American (AMR) AF: 0.347 AC: 5296 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1537 AN: 3472

East Asian (EAS) AF: 0.136 AC: 701 AN: 5170

South Asian (SAS) AF: 0.280 AC: 1349 AN: 4826

European-Finnish (FIN) AF: 0.348 AC: 3668 AN: 10546

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28288 AN: 67976

Other (OTH) AF: 0.343 AC: 723 AN: 2106

Alfa AF: 0.374 Hom.: 26224

Bravo AF: 0.298

Asia WGS AF: 0.209 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.68
PhyloP100		-0.59
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: rs11852861; hg19: chr15-58836308;