rs343

chr8-19953276-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.430-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 1,316,296 control chromosomes in the GnomAD database, including 5,672 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (614 hom., cov: 33)
  • Exomes 𝑓: 0.090 (5058 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.510

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=-0.87).
• BP6: Variant 8-19953276-C-A is Benign according to our data. Variant chr8-19953276-C-A is described in ClinVar as [Benign]. Clinvar id is 1230139.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19953276-C-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.430-34C>A		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.430-34C>A		intron_variant			NM_000237.3	P1
LPL	ENST00000520959.5	c.202-34C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12729 AN: 152086 Hom.: 611 Cov.: 33

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0824

Gnomad OTH AF: 0.0952

GnomAD3 exomes AF: 0.0984 AC: 24640 AN: 250484 Hom.: 1363 AF XY: 0.0999 AC XY: 13533 AN XY: 135412

Gnomad AFR exome AF: 0.0498

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.0649

Gnomad NFE exome AF: 0.0813

Gnomad OTH exome AF: 0.0987

GnomAD4 exome AF: 0.0903 AC: 105163 AN: 1164092 Hom.: 5058 Cov.: 16 AF XY: 0.0924 AC XY: 54806 AN XY: 593430

Gnomad4 AFR exome AF: 0.0496

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.137

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0635

Gnomad4 NFE exome AF: 0.0838

Gnomad4 OTH exome AF: 0.0931

GnomAD4 genome AF: 0.0837 AC: 12733 AN: 152204 Hom.: 614 Cov.: 33 AF XY: 0.0859 AC XY: 6392 AN XY: 74426

Gnomad4 AFR AF: 0.0514

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.0824

Gnomad4 OTH AF: 0.0975

Alfa AF: 0.0912 Hom.: 690

Bravo AF: 0.0861

Asia WGS AF: 0.145 AC: 502 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.49
Dann	Benign	0.17

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: rs343; hg19: chr8-19810787; COSMIC: COSV60930528; COSMIC: COSV60930528;