rs6076

Positions:

• chr15-58541739-G-A
• chr15-58541739-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000236.3(LIPC):​c.274-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,573,188 control chromosomes in the GnomAD database, including 49,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5886 hom., cov: 31)
  • Exomes 𝑓: 0.21 (43387 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.975

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 15-58541739-G-A is Benign according to our data. Variant chr15-58541739-G-A is described in ClinVar as [Benign]. Clinvar id is 1261952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-58541739-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.274-46G>A		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.274-46G>A		intron_variant		1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37771 AN: 151874 Hom.: 5871 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.295 AC: 67608 AN: 229226 Hom.: 13662 AF XY: 0.285 AC XY: 35307 AN XY: 123780

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.214 AC: 303763 AN: 1421196 Hom.: 43387 Cov.: 27 AF XY: 0.216 AC XY: 152541 AN XY: 707432

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.450

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.796

Gnomad4 SAS exome AF: 0.336

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.249 AC: 37836 AN: 151992 Hom.: 5886 Cov.: 31 AF XY: 0.262 AC XY: 19473 AN XY: 74284

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.766

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.243

Alfa AF: 0.186 Hom.: 2711

Bravo AF: 0.254

Asia WGS AF: 0.574 AC: 1990 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.99
CADD	Benign	0.025
DANN	Benign	0.78

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: rs6076; hg19: chr15-58833938;