rs270

chr8-19956165-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):c.1018+82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,573,220 control chromosomes in the GnomAD database, including 19,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1691 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17801 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.526

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-19956165-C-A is Benign according to our data. Variant chr8-19956165-C-A is described in ClinVar as [Benign]. Clinvar id is 1227345.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19956165-C-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.1018+82C>A		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.1018+82C>A		intron_variant			NM_000237.3	P1
LPL	ENST00000650478.1	c.79+82C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21543 AN: 152102 Hom.: 1692 Cov.: 33

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.156 AC: 221079 AN: 1421000 Hom.: 17801 AF XY: 0.154 AC XY: 109491 AN XY: 709014

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0984

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.142 AC: 21552 AN: 152220 Hom.: 1691 Cov.: 33 AF XY: 0.143 AC XY: 10611 AN XY: 74406

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.134

Alfa AF: 0.152 Hom.: 2508

Bravo AF: 0.135

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperlipoproteinemia, type I Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Aug 28, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	9.1
Dann	Benign	0.67

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: rs270; hg19: chr8-19813676;