chr8-19937893-C-T

Variant names:

• chr8-19937893-C-T
• rs17091738
• ENST00000520959.5:c.-140-10287C>T

Variant summary

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

The ENST00000520959.5(LPL):​c.-140-10287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0668 in 152,146 control chromosomes in the GnomAD database, including 848 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 0.067 (848 hom., cov: 32)
• Consequence: LPL ENST00000520959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000520959.5	c.-140-10287C>T		intron_variant	Intron 1 of 4	4		ENSP00000428496.1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10123 AN: 152028 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0322

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0608

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

GnomAD4 genome AF: 0.0668 AC: 10161 AN: 152146 Hom.: 848 Cov.: 32 AF XY: 0.0652 AC XY: 4849 AN XY: 74372

African (AFR) AF: 0.198 AC: 8220 AN: 41476

American (AMR) AF: 0.0304 AC: 465 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3468

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0314 AC: 151 AN: 4816

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10592

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1131 AN: 68004

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0554 Hom.: 104

Bravo AF: 0.0744

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.42
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17091738; hg19: chr8-19795404;