8-19944891-C-T

Variant names:

• chr8-19944891-C-T
• rs10104051
• NM_000237.3:c.89-3289C>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.89-3289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,054 control chromosomes in the GnomAD database, including 23,646 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 0.52 (23646 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 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.89-3289C>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.89-3289C>T		intron	N/A	ENSP00000497642.1
	LPL	ENST00000524029.5	TSL:4	c.89-3289C>T		intron	N/A	ENSP00000428237.1
	LPL	ENST00000520959.5	TSL:4	c.-140-3289C>T		intron	N/A	ENSP00000428496.1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78802 AN: 151936 Hom.: 23597 Cov.: 32

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.519 AC: 78906 AN: 152054 Hom.: 23646 Cov.: 32 AF XY: 0.511 AC XY: 38001 AN XY: 74326

African (AFR) AF: 0.830 AC: 34440 AN: 41490

American (AMR) AF: 0.362 AC: 5533 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3470

East Asian (EAS) AF: 0.159 AC: 823 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4567 AN: 10546

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 28997 AN: 67980

Other (OTH) AF: 0.458 AC: 968 AN: 2112

Alfa AF: 0.483 Hom.: 3183

Bravo AF: 0.521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.45
PhyloP100		0.071

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: rs10104051; hg19: chr8-19802402;