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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine

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.

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.1437C>A	p.Thr479Thr	synonymous	Exon 9 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.1437C>A	p.Thr479Thr	synonymous	Exon 9 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000901642.1		c.1542C>A	p.Thr514Thr	synonymous	Exon 11 of 11	ENSP00000571701.1
	LIPC	ENST00000901654.1		c.1542C>A	p.Thr514Thr	synonymous	Exon 11 of 11	ENSP00000571713.1

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

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	-0.26
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;