rs319

Positions:

• chr8-19961465-A-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-19961465-A-C is Benign according to our data. Variant chr8-19961465-A-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1322+382A>C		intron_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1322+382A>C		intron_variant			NM_000237.3	ENSP00000497642	P1
LPL	ENST00000650478.1	c.*145+382A>C		intron_variant, NMD_transcript_variant				ENSP00000497560

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.178

Alfa AF: 0.221 Hom.: 3547

Bravo AF: 0.180

Asia WGS AF: 0.112 AC: 390 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	5.0
DANN	Benign	0.72

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: rs319; hg19: chr8-19818976;