rs319

Variant names:

• chr8-19961465-A-C
• rs319
• NM_000237.3:c.1322+382A>C

Variant summary

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

The NM_000237.3(LPL):​c.1322+382A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 151,874 control chromosomes in the GnomAD database, including 3,163 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 0.19 (3163 hom., cov: 30)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 9 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, 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 (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.1322+382A>C		intron	N/A	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.1322+382A>C		intron	N/A	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.1322+382A>C		intron	N/A	ENSP00000635987.1
	LPL	ENST00000965929.1		c.1319+382A>C		intron	N/A	ENSP00000635988.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28995 AN: 151758 Hom.: 3165 Cov.: 30

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.191 AC: 28998 AN: 151874 Hom.: 3163 Cov.: 30 AF XY: 0.191 AC XY: 14206 AN XY: 74248

African (AFR) AF: 0.109 AC: 4535 AN: 41434

American (AMR) AF: 0.184 AC: 2803 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 423 AN: 3464

East Asian (EAS) AF: 0.128 AC: 661 AN: 5158

South Asian (SAS) AF: 0.144 AC: 686 AN: 4772

European-Finnish (FIN) AF: 0.304 AC: 3200 AN: 10538

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16075 AN: 67930

Other (OTH) AF: 0.178 AC: 375 AN: 2110

Alfa AF: 0.216 Hom.: 4574

Bravo AF: 0.180

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.72
PhyloP100		0.52

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: rs319; hg19: chr8-19818976;