rs249

Positions:

• chr8-19953495-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.541+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 1,103,958 control chromosomes in the GnomAD database, including 3,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (710 hom., cov: 33)
  • Exomes 𝑓: 0.078 (3043 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

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=-0.84).
• BP6: Variant 8-19953495-T-C is Benign according to our data. Variant chr8-19953495-T-C is described in ClinVar as [Benign]. Clinvar id is 1237990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19953495-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPL	NM_000237.3	c.541+74T>C		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.541+74T>C		intron_variant			NM_000237.3	P1
LPL	ENST00000520959.5	c.313+74T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13416 AN: 147252 Hom.: 711 Cov.: 33

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0302

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0664

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.100

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.0799

GnomAD4 exome AF: 0.0775 AC: 74180 AN: 956606 Hom.: 3043 AF XY: 0.0784 AC XY: 38890 AN XY: 496098

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0359

Gnomad4 ASJ exome AF: 0.0425

Gnomad4 EAS exome AF: 0.0704

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0799

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.0910 AC: 13413 AN: 147352 Hom.: 710 Cov.: 33 AF XY: 0.0893 AC XY: 6434 AN XY: 72074

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0561

Gnomad4 ASJ AF: 0.0403

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0805

Gnomad4 OTH AF: 0.0787

Alfa AF: 0.0856 Hom.: 152

Bravo AF: 0.0882

Asia WGS AF: 0.0880 AC: 305 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 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.59

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: rs249; hg19: chr8-19811006;