rs2242061

Variant names:

• chr15-58542176-T-C
• rs2242061
• NM_000236.3:c.456+209T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000236.3(LIPC):​c.456+209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,848 control chromosomes in the GnomAD database, including 6,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6599 hom., cov: 31)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.567
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 15-58542176-T-C is Benign according to our data. Variant chr15-58542176-T-C is described in ClinVar as [Benign]. Clinvar id is 1225442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.456+209T>C		intron_variant	Intron 3 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.456+209T>C		intron_variant	Intron 3 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43477 AN: 151730 Hom.: 6590 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.287 AC: 43523 AN: 151848 Hom.: 6599 Cov.: 31 AF XY: 0.295 AC XY: 21848 AN XY: 74180

African (AFR) AF: 0.255 AC: 10566 AN: 41416

American (AMR) AF: 0.380 AC: 5785 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.457 AC: 2346 AN: 5134

South Asian (SAS) AF: 0.383 AC: 1837 AN: 4802

European-Finnish (FIN) AF: 0.367 AC: 3870 AN: 10536

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17345 AN: 67932

Other (OTH) AF: 0.281 AC: 594 AN: 2114

Alfa AF: 0.249 Hom.: 2265

Bravo AF: 0.286

Asia WGS AF: 0.423 AC: 1469 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.84
PhyloP100		-0.57
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: rs2242061; hg19: chr15-58834375; COSMIC: COSV107334512;