rs301

Positions:

• chr8-19959423-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):​c.1139+43T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,607,608 control chromosomes in the GnomAD database, including 45,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4970 hom., cov: 31)
  • Exomes 𝑓: 0.24 (40525 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.14

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-19959423-T-C is Benign according to our data. Variant chr8-19959423-T-C is described in ClinVar as [Benign]. Clinvar id is 1278475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19959423-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1139+43T>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.1139+43T>C		intron_variant			NM_000237.3	ENSP00000497642	P1
LPL	ENST00000650478.1	c.80-1478T>C		intron_variant, NMD_transcript_variant				ENSP00000497560

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38561 AN: 151894 Hom.: 4962 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.238

GnomAD3 exomes AF: 0.242 AC: 58705 AN: 242970 Hom.: 7026 AF XY: 0.240 AC XY: 31594 AN XY: 131896

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.233

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.236

GnomAD4 exome AF: 0.235 AC: 342332 AN: 1455596 Hom.: 40525 Cov.: 32 AF XY: 0.235 AC XY: 170364 AN XY: 723906

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.254 AC: 38583 AN: 152012 Hom.: 4970 Cov.: 31 AF XY: 0.252 AC XY: 18700 AN XY: 74306

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.239

Alfa AF: 0.243 Hom.: 5803

Bravo AF: 0.254

Asia WGS AF: 0.232 AC: 804 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.95
CADD	Benign	0.081
DANN	Benign	0.46

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: rs301; hg19: chr8-19816934; COSMIC: COSV60930545;