Variant rs301 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.14

Variant links:

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]

LPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
LPL	NM_000237.3 linkuse as main transcript	c.1139+43T>C		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1 linkuse as main transcript	c.1139+43T>C		intron_variant			NM_000237.3	P1
LPL	ENST00000650478.1 linkuse as main transcript	c.80-1478T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38561

AN:

151894

Hom.:

4962

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.235

AC XY:

170364

AN XY:

723906

show subpopulations

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.:

AF XY:

0.252

AC XY:

18700

AN XY:

74306

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.95

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over