rs6084

Variant names:

• chr15-58545839-C-G
• rs6084
• NM_000236.3:c.672C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58545839-C-G
• chr15-58545839-C-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.672C>G​(p.Thr224Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,613,898 control chromosomes in the GnomAD database, including 186,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14216 hom., cov: 33)
  • Exomes 𝑓: 0.48 (172007 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.587
• Publications: 34 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=-0.69).
• BP6: Variant 15-58545839-C-G is Benign according to our data. Variant chr15-58545839-C-G is described in ClinVar as Benign. ClinVar VariationId is 316666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.587 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 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.672C>G	p.Thr224Thr	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.672C>G	p.Thr224Thr	synonymous	Exon 5 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.672C>G	p.Thr224Thr	synonymous	Exon 6 of 10	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.529C>G		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62365 AN: 152008 Hom.: 14216 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.0732

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.457

GnomAD2 exomes AF: 0.426 AC: 107114 AN: 251466 AF XY: 0.435

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.552

Gnomad EAS exome AF: 0.0749

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.480

GnomAD4 exome AF: 0.476 AC: 695079 AN: 1461772 Hom.: 172007 Cov.: 47 AF XY: 0.475 AC XY: 345441 AN XY: 727194

African (AFR) AF: 0.241 AC: 8068 AN: 33480

American (AMR) AF: 0.382 AC: 17098 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14452 AN: 26136

East Asian (EAS) AF: 0.0520 AC: 2066 AN: 39698

South Asian (SAS) AF: 0.382 AC: 32968 AN: 86252

European-Finnish (FIN) AF: 0.433 AC: 23140 AN: 53408

Middle Eastern (MID) AF: 0.551 AC: 3180 AN: 5768

European-Non Finnish (NFE) AF: 0.509 AC: 566366 AN: 1111920

Other (OTH) AF: 0.459 AC: 27741 AN: 60386

GnomAD4 genome AF: 0.410 AC: 62393 AN: 152126 Hom.: 14216 Cov.: 33 AF XY: 0.404 AC XY: 30076 AN XY: 74356

African (AFR) AF: 0.250 AC: 10388 AN: 41494

American (AMR) AF: 0.422 AC: 6445 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1903 AN: 3470

East Asian (EAS) AF: 0.0730 AC: 378 AN: 5178

South Asian (SAS) AF: 0.367 AC: 1771 AN: 4824

European-Finnish (FIN) AF: 0.435 AC: 4604 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35328 AN: 67984

Other (OTH) AF: 0.452 AC: 956 AN: 2114

Alfa AF: 0.480 Hom.: 13125

Bravo AF: 0.401

Asia WGS AF: 0.241 AC: 843 AN: 3478

EpiCase AF: 0.532

EpiControl AF: 0.540

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	-0.69
CADD	Benign	5.0
DANN	Benign	0.47
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6084; hg19: chr15-58838038; COSMIC: COSV54420270;