rs1059507

chr8-19966452-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):c.*1142C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,130 control chromosomes in the GnomAD database, including 1,684 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1684 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0410

Genes affected

LPL (HGNC:6677): (lipoprotein lipase) LPL encodes lipoprotein lipase, which is expressed in heart, muscle, and adipose tissue. LPL functions as a homodimer, and has the dual functions of triglyceride hydrolase and ligand/bridging factor for receptor-mediated lipoprotein uptake. Severe mutations that cause LPL deficiency result in type I hyperlipoproteinemia, while less extreme mutations in LPL are linked to many disorders of lipoprotein metabolism. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-19966452-C-T is Benign according to our data. Variant chr8-19966452-C-T is described in ClinVar as [Benign]. Clinvar id is 362436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.*1142C>T		3_prime_UTR_variant	10/10	ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.*1142C>T		3_prime_UTR_variant	10/10		NM_000237.3	P1
LPL	ENST00000650478.1	c.*1393C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22082 AN: 152012 Hom.: 1682 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0947

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.143

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.145 AC: 22091 AN: 152130 Hom.: 1684 Cov.: 32 AF XY: 0.145 AC XY: 10786 AN XY: 74372

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0947

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.145

Alfa AF: 0.149 Hom.: 248

Bravo AF: 0.144

Asia WGS AF: 0.124 AC: 430 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hyperlipoproteinemia, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.4
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs1059507; hg19: chr8-19823963;