rs6076

Variant names:

• chr15-58541739-G-A
• rs6076
• NM_000236.3:c.274-46G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-58541739-G-A
• chr15-58541739-G-C
• chr15-58541739-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000236.3(LIPC):​c.274-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,573,188 control chromosomes in the GnomAD database, including 49,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5886 hom., cov: 31)
  • Exomes 𝑓: 0.21 (43387 hom.)
• Consequence: LIPC NM_000236.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.975
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 15-58541739-G-A is Benign according to our data. Variant chr15-58541739-G-A is described in ClinVar as Benign. ClinVar VariationId is 1261952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPC	NM_000236.3	c.274-46G>A		intron_variant	Intron 2 of 8	ENST00000299022.10	NP_000227.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPC	ENST00000299022.10	c.274-46G>A		intron_variant	Intron 2 of 8	1	NM_000236.3	ENSP00000299022.5

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37771 AN: 151874 Hom.: 5871 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.238

GnomAD2 exomes AF: 0.295 AC: 67608 AN: 229226 AF XY: 0.285

Gnomad AFR exome AF: 0.263

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.778

Gnomad FIN exome AF: 0.310

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.214 AC: 303763 AN: 1421196 Hom.: 43387 Cov.: 27 AF XY: 0.216 AC XY: 152541 AN XY: 707432

African (AFR) AF: 0.260 AC: 8493 AN: 32714

American (AMR) AF: 0.450 AC: 19283 AN: 42850

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4663 AN: 25622

East Asian (EAS) AF: 0.796 AC: 31154 AN: 39160

South Asian (SAS) AF: 0.336 AC: 27925 AN: 83162

European-Finnish (FIN) AF: 0.303 AC: 15752 AN: 51960

Middle Eastern (MID) AF: 0.165 AC: 785 AN: 4768

European-Non Finnish (NFE) AF: 0.168 AC: 181982 AN: 1082048

Other (OTH) AF: 0.233 AC: 13726 AN: 58912

GnomAD4 genome AF: 0.249 AC: 37836 AN: 151992 Hom.: 5886 Cov.: 31 AF XY: 0.262 AC XY: 19473 AN XY: 74284

African (AFR) AF: 0.256 AC: 10597 AN: 41444

American (AMR) AF: 0.348 AC: 5327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 652 AN: 3470

East Asian (EAS) AF: 0.766 AC: 3946 AN: 5152

South Asian (SAS) AF: 0.360 AC: 1729 AN: 4808

European-Finnish (FIN) AF: 0.319 AC: 3367 AN: 10550

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11578 AN: 67964

Other (OTH) AF: 0.243 AC: 513 AN: 2108

Alfa AF: 0.200 Hom.: 3873

Bravo AF: 0.254

Asia WGS AF: 0.574 AC: 1990 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.025
DANN	Benign	0.78
PhyloP100		-0.97
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: rs6076; hg19: chr15-58833938;