ENST00000414170.7:c.*456A>T

Variant names:

• chr15-58565746-A-T
• rs3829460
• ENST00000414170.7:c.*456A>T

Variant summary

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

The ENST00000414170.7(LIPC):​c.*456A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 991,876 control chromosomes in the GnomAD database, including 234,532 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 0.60 (28888 hom., cov: 31)
  • Exomes 𝑓: 0.70 (205644 hom.)
• Consequence: LIPC ENST00000414170.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414170.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.1388+2023A>T		intron	N/A	NP_000227.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000414170.7	TSL:1	c.*456A>T		3_prime_UTR	Exon 10 of 10	ENSP00000395569.3
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.1388+2023A>T		intron	N/A	ENSP00000299022.5
	LIPC	ENST00000356113.10	TSL:2	c.1388+2023A>T		intron	N/A	ENSP00000348425.6

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90665 AN: 151814 Hom.: 28885 Cov.: 31

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.640

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.697 AC: 585841 AN: 839940 Hom.: 205644 Cov.: 31 AF XY: 0.699 AC XY: 271224 AN XY: 388234

African (AFR) AF: 0.360 AC: 5752 AN: 15970

American (AMR) AF: 0.667 AC: 1274 AN: 1910

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 3732 AN: 5302

East Asian (EAS) AF: 0.427 AC: 1668 AN: 3902

South Asian (SAS) AF: 0.756 AC: 12877 AN: 17028

European-Finnish (FIN) AF: 0.729 AC: 360 AN: 494

Middle Eastern (MID) AF: 0.689 AC: 1135 AN: 1648

European-Non Finnish (NFE) AF: 0.706 AC: 540704 AN: 766024

Other (OTH) AF: 0.663 AC: 18339 AN: 27662

GnomAD4 genome AF: 0.597 AC: 90700 AN: 151936 Hom.: 28888 Cov.: 31 AF XY: 0.600 AC XY: 44561 AN XY: 74236

African (AFR) AF: 0.373 AC: 15421 AN: 41390

American (AMR) AF: 0.633 AC: 9659 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2435 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2176 AN: 5154

South Asian (SAS) AF: 0.730 AC: 3517 AN: 4818

European-Finnish (FIN) AF: 0.714 AC: 7530 AN: 10546

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47960 AN: 67980

Other (OTH) AF: 0.608 AC: 1280 AN: 2106

Alfa AF: 0.646 Hom.: 3877

Bravo AF: 0.577

Asia WGS AF: 0.557 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.50
PhyloP100		1.1
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: rs3829460; hg19: chr15-58857945;