rs3751542

chr15-58563834-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000236.3(LIPC):c.1388+111T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 899,372 control chromosomes in the GnomAD database, including 47,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10215 hom., cov: 32)
  • Exomes 𝑓: 0.31 (37111 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.577

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-58563834-T-C is Benign according to our data. Variant chr15-58563834-T-C is described in ClinVar as [Benign]. Clinvar id is 1264051.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-58563834-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPC	NM_000236.3	c.1388+111T>C		intron_variant		ENST00000299022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPC	ENST00000299022.10	c.1388+111T>C		intron_variant		1	NM_000236.3	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53852 AN: 151920 Hom.: 10212 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.358

GnomAD4 exome AF: 0.306 AC: 228493 AN: 747334 Hom.: 37111 Cov.: 10 AF XY: 0.300 AC XY: 117743 AN XY: 391948

Gnomad4 AFR exome AF: 0.465

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.291

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.355 AC: 53899 AN: 152038 Hom.: 10215 Cov.: 32 AF XY: 0.353 AC XY: 26242 AN XY: 74314

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.572

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.360

Alfa AF: 0.316 Hom.: 4673

Bravo AF: 0.368

Asia WGS AF: 0.424 AC: 1472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.63
Dann	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs3751542; hg19: chr15-58856033;