rs314

Variant names:

• chr8-19960531-G-A
• rs314
• NM_000237.3:c.1140-370G>A

Variant summary

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

The NM_000237.3(LPL):​c.1140-370G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,962 control chromosomes in the GnomAD database, including 13,852 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 0.39 (13852 hom., cov: 31)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1140-370G>A		intron_variant	Intron 7 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1140-370G>A		intron_variant	Intron 7 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.80-370G>A		intron_variant	Intron 1 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59095 AN: 151844 Hom.: 13814 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.389 AC: 59178 AN: 151962 Hom.: 13852 Cov.: 31 AF XY: 0.383 AC XY: 28486 AN XY: 74286

African (AFR) AF: 0.665 AC: 27521 AN: 41416

American (AMR) AF: 0.311 AC: 4755 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3466

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5174

South Asian (SAS) AF: 0.275 AC: 1328 AN: 4830

European-Finnish (FIN) AF: 0.249 AC: 2628 AN: 10544

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.285 AC: 19339 AN: 67946

Other (OTH) AF: 0.360 AC: 759 AN: 2110

Alfa AF: 0.466 Hom.: 4388

Bravo AF: 0.403

Asia WGS AF: 0.289 AC: 1001 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.43
PhyloP100		-1.3

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: rs314; hg19: chr8-19818042;