rs6074

Variant names:

• chr15-58568764-C-A
• rs6074
• NM_000236.3:c.1437C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-58568764-C-A
• chr15-58568764-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000236.3(LIPC):​c.1437C>A​(p.Thr479Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,608,476 control chromosomes in the GnomAD database, including 24,583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T479T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.15 (1950 hom., cov: 33)
  • Exomes 𝑓: 0.16 (22633 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.24
• Publications: 26 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 15-58568764-C-A is Benign according to our data. Variant chr15-58568764-C-A is described in ClinVar as Benign. ClinVar VariationId is 316681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.1437C>A	p.Thr479Thr	synonymous_variant	Exon 9 of 9	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.1437C>A	p.Thr479Thr	synonymous_variant	Exon 9 of 9	1	NM_000236.3	ENSP00000299022.5
LIPC	ENST00000356113.10	c.1437C>A	p.Thr479Thr	synonymous_variant	Exon 11 of 11	2		ENSP00000348425.6
LIPC	ENST00000433326.2	c.1254C>A	p.Thr418Thr	synonymous_variant	Exon 8 of 8	2		ENSP00000395002.2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22208 AN: 151956 Hom.: 1944 Cov.: 33

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.193 AC: 48231 AN: 250016 AF XY: 0.196

Gnomad AFR exome AF: 0.0930

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.0997

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.170

GnomAD4 exome AF: 0.165 AC: 239746 AN: 1456404 Hom.: 22633 Cov.: 30 AF XY: 0.169 AC XY: 122784 AN XY: 724748

African (AFR) AF: 0.0945 AC: 3153 AN: 33348

American (AMR) AF: 0.248 AC: 11052 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2700 AN: 26100

East Asian (EAS) AF: 0.281 AC: 11125 AN: 39524

South Asian (SAS) AF: 0.340 AC: 29170 AN: 85870

European-Finnish (FIN) AF: 0.244 AC: 12970 AN: 53140

Middle Eastern (MID) AF: 0.106 AC: 610 AN: 5762

European-Non Finnish (NFE) AF: 0.144 AC: 159800 AN: 1107844

Other (OTH) AF: 0.152 AC: 9166 AN: 60176

GnomAD4 genome AF: 0.146 AC: 22216 AN: 152072 Hom.: 1950 Cov.: 33 AF XY: 0.155 AC XY: 11487 AN XY: 74338

African (AFR) AF: 0.0914 AC: 3789 AN: 41476

American (AMR) AF: 0.175 AC: 2677 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 362 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1341 AN: 5170

South Asian (SAS) AF: 0.336 AC: 1616 AN: 4816

European-Finnish (FIN) AF: 0.242 AC: 2553 AN: 10562

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9551 AN: 67966

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.137 Hom.: 4943

Bravo AF: 0.136

Asia WGS AF: 0.273 AC: 946 AN: 3476

EpiCase AF: 0.129

EpiControl AF: 0.123

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hyperlipidemia due to hepatic triglyceride lipase deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs6074; hg19: chr15-58860963; COSMIC: COSV54422234; COSMIC: COSV54422234;