rs17091738

Positions:

• chr8-19937893-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000520959.5	c.-140-10287C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0314

Gnomad4 FIN AF: 0.00189

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0501 Hom.: 88

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17091738; hg19: chr8-19795404;