rs255

chr8-19954390-T-C

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.775+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,581,682 control chromosomes in the GnomAD database, including 20,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2545 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17824 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0960

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=-0.83).
• BP6: Variant 8-19954390-T-C is Benign according to our data. Variant chr8-19954390-T-C is described in ClinVar as [Benign]. Clinvar id is 1182670.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19954390-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.775+37T>C		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.775+37T>C		intron_variant			NM_000237.3	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26799 AN: 152036 Hom.: 2533 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.167 AC: 41243 AN: 247204 Hom.: 3574 AF XY: 0.168 AC XY: 22481 AN XY: 133784

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.157

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.224

Gnomad SAS exome AF: 0.222

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.155 AC: 221787 AN: 1429528 Hom.: 17824 Cov.: 26 AF XY: 0.157 AC XY: 112071 AN XY: 713296

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.176 AC: 26835 AN: 152154 Hom.: 2545 Cov.: 33 AF XY: 0.176 AC XY: 13104 AN XY: 74396

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.168

Alfa AF: 0.168 Hom.: 719

Bravo AF: 0.181

Asia WGS AF: 0.234 AC: 813 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

Apr 01, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.8
Dann	Benign	0.27

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: rs255; hg19: chr8-19811901; COSMIC: COSV60929933; COSMIC: COSV60929933;