rs6082

Variant names:

• chr15-58545758-A-G
• rs6082
• NM_000236.3:c.591A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58545758-A-G
• chr15-58545758-A-T

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.591A>G​(p.Gly197Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 1,613,402 control chromosomes in the GnomAD database, including 11,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1148 hom., cov: 34)
  • Exomes 𝑓: 0.097 (10164 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.09
• Publications: 22 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=-0.84).
• BP6: Variant 15-58545758-A-G is Benign according to our data. Variant chr15-58545758-A-G is described in ClinVar as Benign. ClinVar VariationId is 316664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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.591A>G	p.Gly197Gly	synonymous	Exon 5 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.591A>G	p.Gly197Gly	synonymous	Exon 5 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.591A>G	p.Gly197Gly	synonymous	Exon 6 of 10	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.448A>G		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15825 AN: 151996 Hom.: 1148 Cov.: 34

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.128 AC: 32071 AN: 251258 AF XY: 0.121

Gnomad AFR exome AF: 0.0918

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.0790

Gnomad EAS exome AF: 0.418

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.0781

Gnomad OTH exome AF: 0.0971

GnomAD4 exome AF: 0.0974 AC: 142273 AN: 1461288 Hom.: 10164 Cov.: 40 AF XY: 0.0966 AC XY: 70260 AN XY: 727006

African (AFR) AF: 0.0883 AC: 2957 AN: 33472

American (AMR) AF: 0.201 AC: 8987 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 2138 AN: 26132

East Asian (EAS) AF: 0.441 AC: 17495 AN: 39694

South Asian (SAS) AF: 0.105 AC: 9048 AN: 86250

European-Finnish (FIN) AF: 0.109 AC: 5833 AN: 53398

Middle Eastern (MID) AF: 0.0650 AC: 374 AN: 5758

European-Non Finnish (NFE) AF: 0.0800 AC: 88922 AN: 1111484

Other (OTH) AF: 0.108 AC: 6519 AN: 60378

GnomAD4 genome AF: 0.104 AC: 15840 AN: 152114 Hom.: 1148 Cov.: 34 AF XY: 0.108 AC XY: 8030 AN XY: 74342

African (AFR) AF: 0.0913 AC: 3791 AN: 41510

American (AMR) AF: 0.151 AC: 2315 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2145 AN: 5158

South Asian (SAS) AF: 0.121 AC: 582 AN: 4804

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10576

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0781 AC: 5308 AN: 67998

Other (OTH) AF: 0.107 AC: 225 AN: 2108

Alfa AF: 0.0849 Hom.: 1451

Bravo AF: 0.112

Asia WGS AF: 0.271 AC: 941 AN: 3478

EpiCase AF: 0.0766

EpiControl AF: 0.0719

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.43
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs6082; hg19: chr15-58837957; COSMIC: COSV54422892;