rs1869129

Variant names:

• chr15-58561164-C-T
• rs1869129
• NM_000236.3:c.1169+183C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-58561164-C-T
• chr15-58561164-C-A

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.1169+183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,238 control chromosomes in the GnomAD database, including 65,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.92 (65667 hom., cov: 33)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.772
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 15-58561164-C-T is Benign according to our data. Variant chr15-58561164-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	NM_000236.3	MANE Select	c.1169+183C>T		intron	N/A	NP_000227.2	P11150

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPC	ENST00000299022.10	TSL:1 MANE Select	c.1169+183C>T		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.1169+183C>T		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.1026+183C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.925 AC: 140757 AN: 152120 Hom.: 65652 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 0.937

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.941

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

GnomAD4 genome AF: 0.925 AC: 140809 AN: 152238 Hom.: 65667 Cov.: 33 AF XY: 0.926 AC XY: 68931 AN XY: 74448

African (AFR) AF: 0.787 AC: 32649 AN: 41504

American (AMR) AF: 0.973 AC: 14886 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3429 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4854 AN: 5184

South Asian (SAS) AF: 0.985 AC: 4757 AN: 4830

European-Finnish (FIN) AF: 0.947 AC: 10036 AN: 10602

Middle Eastern (MID) AF: 0.976 AC: 285 AN: 292

European-Non Finnish (NFE) AF: 0.985 AC: 67013 AN: 68026

Other (OTH) AF: 0.942 AC: 1988 AN: 2110

Alfa AF: 0.944 Hom.: 8813

Bravo AF: 0.921

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.19
PhyloP100		0.77
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: rs1869129; hg19: chr15-58853363;