rs17190678

Positions:

• chr15-58555173-C-G
• chr15-58555173-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000236.3(LIPC):​c.1052-5691C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,134 control chromosomes in the GnomAD database, including 14,562 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 0.41 (14562 hom., cov: 33)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPC	NM_000236.3	c.1052-5691C>G		intron_variant		ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.1052-5691C>G		intron_variant		1	NM_000236.3	ENSP00000299022	P1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61863 AN: 152016 Hom.: 14566 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.407 AC: 61876 AN: 152134 Hom.: 14562 Cov.: 33 AF XY: 0.402 AC XY: 29920 AN XY: 74368

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.0963

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.451

Alfa AF: 0.461 Hom.: 2138

Bravo AF: 0.394

Asia WGS AF: 0.262 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.0
DANN	Benign	0.39

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: rs17190678; hg19: chr15-58847372;