rs3829461

Variant names:

• chr15-58560910-A-G
• rs3829461
• NM_000236.3:c.1098A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-58560910-A-G
• chr15-58560910-A-C
• chr15-58560910-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.1098A>G​(p.Thr366Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.975 in 1,530,340 control chromosomes in the GnomAD database, including 728,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68368 hom., cov: 32)
  • Exomes 𝑓: 0.98 (659876 hom.)
• Consequence: LIPC NM_000236.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.123
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-58560910-A-G is Benign according to our data. Variant chr15-58560910-A-G is described in ClinVar as Benign. ClinVar VariationId is 316674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.123 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.979 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.1098A>G	p.Thr366Thr	synonymous	Exon 7 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.1098A>G	p.Thr366Thr	synonymous	Exon 7 of 9	ENSP00000299022.5	P11150
	LIPC	ENST00000414170.7	TSL:1	c.1098A>G	p.Thr366Thr	synonymous	Exon 8 of 10	ENSP00000395569.3	E7EUJ1
	LIPC	ENST00000559845.5	TSL:1	n.955A>G		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143958 AN: 152152 Hom.: 68334 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.947

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.966

GnomAD2 exomes AF: 0.972 AC: 244309 AN: 251330 AF XY: 0.975

Gnomad AFR exome AF: 0.860

Gnomad AMR exome AF: 0.991

Gnomad ASJ exome AF: 0.997

Gnomad EAS exome AF: 0.942

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.985

Gnomad OTH exome AF: 0.981

GnomAD4 exome AF: 0.978 AC: 1348031 AN: 1378070 Hom.: 659876 Cov.: 25 AF XY: 0.979 AC XY: 675895 AN XY: 690322

African (AFR) AF: 0.855 AC: 27192 AN: 31786

American (AMR) AF: 0.990 AC: 44144 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 25614 AN: 25672

East Asian (EAS) AF: 0.910 AC: 35750 AN: 39266

South Asian (SAS) AF: 0.987 AC: 83466 AN: 84564

European-Finnish (FIN) AF: 0.948 AC: 50603 AN: 53390

Middle Eastern (MID) AF: 0.987 AC: 5548 AN: 5620

European-Non Finnish (NFE) AF: 0.985 AC: 1019566 AN: 1035578

Other (OTH) AF: 0.975 AC: 56148 AN: 57588

GnomAD4 genome AF: 0.946 AC: 144044 AN: 152270 Hom.: 68368 Cov.: 32 AF XY: 0.946 AC XY: 70413 AN XY: 74450

African (AFR) AF: 0.857 AC: 35612 AN: 41538

American (AMR) AF: 0.982 AC: 15018 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.998 AC: 3466 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4848 AN: 5180

South Asian (SAS) AF: 0.987 AC: 4763 AN: 4828

European-Finnish (FIN) AF: 0.947 AC: 10039 AN: 10606

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.986 AC: 67051 AN: 68032

Other (OTH) AF: 0.967 AC: 2046 AN: 2116

Alfa AF: 0.974 Hom.: 293067

Bravo AF: 0.945

Asia WGS AF: 0.962 AC: 3346 AN: 3478

EpiCase AF: 0.987

EpiControl AF: 0.987

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	-0.89
CADD	Benign	0.12
DANN	Benign	0.34
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs3829461; hg19: chr15-58853109; COSMIC: COSV108154886;