rs74304285

Positions:

• chr8-19950519-G-A

Variant summary

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

The NM_000237.3(LPL):​c.250-1250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,200 control chromosomes in the GnomAD database, including 1,413 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 0.13 (1413 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.250-1250G>A		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.250-1250G>A		intron_variant			NM_000237.3	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19438 AN: 152082 Hom.: 1408 Cov.: 32

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.128 AC: 19458 AN: 152200 Hom.: 1413 Cov.: 32 AF XY: 0.128 AC XY: 9531 AN XY: 74404

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.132

Alfa AF: 0.136 Hom.: 292

Bravo AF: 0.122

Asia WGS AF: 0.186 AC: 645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.65

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: rs74304285; hg19: chr8-19808030;