rs690

Variant names:

• chr15-58542542-G-T
• rs690
• NM_000236.3:c.465G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-58542542-G-T
• chr15-58542542-G-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000236.3(LIPC):​c.465G>T​(p.Val155Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,605,242 control chromosomes in the GnomAD database, including 260,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23085 hom., cov: 32)
  • Exomes 𝑓: 0.57 (237249 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.134
• Publications: 43 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-58542542-G-T is Benign according to our data. Variant chr15-58542542-G-T is described in ClinVar as Benign. ClinVar VariationId is 316660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.134 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 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.465G>T	p.Val155Val	synonymous	Exon 4 of 9	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.465G>T	p.Val155Val	synonymous	Exon 4 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.465G>T	p.Val155Val	synonymous	Exon 5 of 10	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.322G>T		non_coding_transcript_exon	Exon 3 of 7

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83070 AN: 151864 Hom.: 23081 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.511

GnomAD2 exomes AF: 0.533 AC: 133986 AN: 251454 AF XY: 0.542

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.589

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.556

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.566 AC: 822296 AN: 1453260 Hom.: 237249 Cov.: 30 AF XY: 0.567 AC XY: 409954 AN XY: 723418

African (AFR) AF: 0.544 AC: 18117 AN: 33284

American (AMR) AF: 0.427 AC: 19093 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 15411 AN: 26078

East Asian (EAS) AF: 0.218 AC: 8649 AN: 39620

South Asian (SAS) AF: 0.582 AC: 50102 AN: 86078

European-Finnish (FIN) AF: 0.552 AC: 29402 AN: 53284

Middle Eastern (MID) AF: 0.569 AC: 3268 AN: 5748

European-Non Finnish (NFE) AF: 0.584 AC: 645200 AN: 1104414

Other (OTH) AF: 0.550 AC: 33054 AN: 60068

GnomAD4 genome AF: 0.547 AC: 83109 AN: 151982 Hom.: 23085 Cov.: 32 AF XY: 0.543 AC XY: 40309 AN XY: 74280

African (AFR) AF: 0.548 AC: 22720 AN: 41442

American (AMR) AF: 0.471 AC: 7203 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1986 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5160

South Asian (SAS) AF: 0.566 AC: 2723 AN: 4812

European-Finnish (FIN) AF: 0.547 AC: 5779 AN: 10564

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39513 AN: 67944

Other (OTH) AF: 0.506 AC: 1063 AN: 2100

Alfa AF: 0.568 Hom.: 54280

Bravo AF: 0.542

Asia WGS AF: 0.352 AC: 1227 AN: 3478

EpiCase AF: 0.596

EpiControl AF: 0.589

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Hyperlipidemia due to hepatic triglyceride lipase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.56
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs690; hg19: chr15-58834741; COSMIC: COSV54420205;