Variant chr8-19965681-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000237.3(LPL):c.*371T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0364 in 197,868 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 173 hom., cov: 32)

Exomes 𝑓: 0.026 ( 31 hom. )

Consequence

LPL
NM_000237.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.06

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-19965681-T-C is Benign according to our data. Variant chr8-19965681-T-C is described in ClinVar as [Benign]. Clinvar id is 362422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19965681-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3 linkuse as main transcript	c.*371T>C		3_prime_UTR_variant	10/10	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1 linkuse as main transcript	c.*371T>C		3_prime_UTR_variant	10/10		NM_000237.3	ENSP00000497642	P1
LPL	ENST00000650478.1 linkuse as main transcript	c.*622T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4			ENSP00000497560

Frequencies

GnomAD3 genomes

AF:

0.0395

AC:

6012

AN:

152152

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0743

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0350

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0417

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0271

Gnomad OTH

AF:

0.0397

GnomAD4 exome

AF:

0.0260

AC:

1185

AN:

45598

Hom.:

Cov.:

AF XY:

0.0258

AC XY:

595

AN XY:

23084

show subpopulations

Gnomad4 AFR exome

AF:

0.0730

Gnomad4 AMR exome

AF:

0.0243

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.0323

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.0273

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0395

AC:

6013

AN:

152270

Hom.:

173

Cov.:

AF XY:

0.0385

AC XY:

2870

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0741

Gnomad4 AMR

AF:

0.0349

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0417

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.0271

Gnomad4 OTH

AF:

0.0388

Alfa

AF:

0.0377

Hom.:

Bravo

AF:

0.0410

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 14, 2019	This variant is associated with the following publications: (PMID: 20650961) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 18, 2023	- -

Hyperlipoproteinemia, type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.76

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