rs17410577

Positions:

• chr8-19942034-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000237.3(LPL):​c.88+2506G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,148 control chromosomes in the GnomAD database, including 2,386 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 0.17 (2386 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.88+2506G>C		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.88+2506G>C		intron_variant			NM_000237.3	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25165 AN: 152030 Hom.: 2385 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0867

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.165 AC: 25167 AN: 152148 Hom.: 2386 Cov.: 32 AF XY: 0.166 AC XY: 12353 AN XY: 74374

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.0864

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.154

Alfa AF: 0.176 Hom.: 311

Bravo AF: 0.155

Asia WGS AF: 0.0520 AC: 181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.7
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs17410577; hg19: chr8-19799545;