8-19942130-G-T

Variant names:

• chr8-19942130-G-T
• rs1534649
• NM_000237.3:c.88+2602G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000237.3(LPL):​c.88+2602G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,078 control chromosomes in the GnomAD database, including 24,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (24562 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 22 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. 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.88+2602G>T		intron	N/A	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.88+2602G>T		intron	N/A	ENSP00000497642.1
	LPL	ENST00000524029.5	TSL:4	c.88+2602G>T		intron	N/A	ENSP00000428237.1
	LPL	ENST00000520959.5	TSL:4	c.-140-6050G>T		intron	N/A	ENSP00000428496.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80577 AN: 151960 Hom.: 24511 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.470

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80683 AN: 152078 Hom.: 24562 Cov.: 32 AF XY: 0.522 AC XY: 38827 AN XY: 74348

African (AFR) AF: 0.838 AC: 34787 AN: 41500

American (AMR) AF: 0.375 AC: 5726 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3470

East Asian (EAS) AF: 0.160 AC: 824 AN: 5166

South Asian (SAS) AF: 0.363 AC: 1751 AN: 4820

European-Finnish (FIN) AF: 0.436 AC: 4609 AN: 10576

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30122 AN: 67950

Other (OTH) AF: 0.469 AC: 991 AN: 2112

Alfa AF: 0.449 Hom.: 24641

Bravo AF: 0.533

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.37

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: rs1534649; hg19: chr8-19799641;