rs1800590

Variant names:

• chr8-19939160-T-G
• rs1800590
• ENST00000524029.5:c.-153-128T>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000524029.5(LPL):​c.-153-128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 516,462 control chromosomes in the GnomAD database, including 3,994 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (3135 hom., cov: 32)
  • Exomes 𝑓: 0.029 (859 hom.)
• Consequence: LPL ENST00000524029.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 0.707
• Publications: 62 publications found

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]

LPL Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 8-19939160-T-G is Benign according to our data. Variant chr8-19939160-T-G is described in ClinVar as Benign. ClinVar VariationId is 362399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524029.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.-281T>G		upstream_gene	N/A	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000524029.5	TSL:4	c.-153-128T>G		intron	N/A	ENSP00000428237.1
	LPL	ENST00000520959.5	TSL:4	c.-140-9020T>G		intron	N/A	ENSP00000428496.1
	LPL	ENST00000522701.5	TSL:4	c.-218-63T>G		intron	N/A	ENSP00000428557.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18284 AN: 151894 Hom.: 3114 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0925

GnomAD4 exome AF: 0.0290 AC: 10563 AN: 364450 Hom.: 859 Cov.: 0 AF XY: 0.0279 AC XY: 5298 AN XY: 190104

African (AFR) AF: 0.378 AC: 3632 AN: 9618

American (AMR) AF: 0.0333 AC: 457 AN: 13730

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 239 AN: 11632

East Asian (EAS) AF: 0.000575 AC: 14 AN: 24354

South Asian (SAS) AF: 0.0350 AC: 1320 AN: 37678

European-Finnish (FIN) AF: 0.00232 AC: 55 AN: 23732

Middle Eastern (MID) AF: 0.0433 AC: 70 AN: 1616

European-Non Finnish (NFE) AF: 0.0172 AC: 3791 AN: 220360

Other (OTH) AF: 0.0453 AC: 985 AN: 21730

GnomAD4 genome AF: 0.121 AC: 18349 AN: 152012 Hom.: 3135 Cov.: 32 AF XY: 0.117 AC XY: 8697 AN XY: 74332

African (AFR) AF: 0.385 AC: 15932 AN: 41388

American (AMR) AF: 0.0487 AC: 744 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5164

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4826

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10602

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0178 AC: 1207 AN: 67978

Other (OTH) AF: 0.0911 AC: 192 AN: 2108

Alfa AF: 0.0755 Hom.: 1878

Bravo AF: 0.136

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hyperlipoproteinemia, type I (1)
-	-	-	Hyperlipidemia, familial combined, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92
PhyloP100		0.71
PromoterAI		-0.087	Neutral

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: rs1800590; hg19: chr8-19796671;