rs3751542

Variant names:

• chr15-58563834-T-C
• rs3751542
• NM_000236.3:c.1388+111T>C

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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.577
• Publications: 7 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=-0.9).
• BP6: Variant 15-58563834-T-C is Benign according to our data. Variant chr15-58563834-T-C is described in ClinVar as Benign. ClinVar VariationId is 1264051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 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.1388+111T>C		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.1388+111T>C		intron	N/A	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.1388+111T>C		intron	N/A	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.1356T>C		non_coding_transcript_exon	Exon 7 of 7

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

African (AFR) AF: 0.465 AC: 8944 AN: 19214

American (AMR) AF: 0.335 AC: 11693 AN: 34940

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 5875 AN: 21206

East Asian (EAS) AF: 0.537 AC: 17629 AN: 32848

South Asian (SAS) AF: 0.249 AC: 16419 AN: 65950

European-Finnish (FIN) AF: 0.283 AC: 10914 AN: 38522

Middle Eastern (MID) AF: 0.295 AC: 839 AN: 2844

European-Non Finnish (NFE) AF: 0.291 AC: 143995 AN: 495144

Other (OTH) AF: 0.332 AC: 12185 AN: 36666

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

African (AFR) AF: 0.462 AC: 19184 AN: 41484

American (AMR) AF: 0.346 AC: 5290 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 953 AN: 3472

East Asian (EAS) AF: 0.572 AC: 2946 AN: 5152

South Asian (SAS) AF: 0.269 AC: 1293 AN: 4806

European-Finnish (FIN) AF: 0.286 AC: 3018 AN: 10568

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 19976 AN: 67958

Other (OTH) AF: 0.360 AC: 761 AN: 2112

Alfa AF: 0.316 Hom.: 4673

Bravo AF: 0.368

Asia WGS AF: 0.424 AC: 1472 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	-0.90
CADD	Benign	0.63
DANN	Benign	0.53
PhyloP100		-0.58
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3751542;

hg19: chr15-58856033;