Variant chr8-19956191-G-A 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.1018+108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,489,690 control chromosomes in the GnomAD database, including 16,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1427 hom., cov: 32)

Exomes 𝑓: 0.15 ( 14719 hom. )

Consequence

LPL
NM_000237.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.495

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=-0.9).

BP6

Variant 8-19956191-G-A is Benign according to our data. Variant chr8-19956191-G-A is described in ClinVar as [Benign]. Clinvar id is 1289075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19956191-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.21 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.1018+108G>A		intron_variant		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.1018+108G>A		intron_variant			NM_000237.3	ENSP00000497642	P1
LPL	ENST00000650478.1 linkuse as main transcript	c.79+108G>A		intron_variant, NMD_transcript_variant				ENSP00000497560

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19272

AN:

152096

Hom.:

1424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.131

GnomAD4 exome

AF:

0.146

AC:

195416

AN:

1337474

Hom.:

14719

AF XY:

0.147

AC XY:

98876

AN XY:

670868

show subpopulations

Gnomad4 AFR exome

AF:

0.0589

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.146

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.127

AC:

19272

AN:

152216

Hom.:

1427

Cov.:

AF XY:

0.128

AC XY:

9500

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0622

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0859

Hom.:

161

Bravo

AF:

0.125

Asia WGS

AF:

0.189

AC:

657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Apr 01, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.34

DANN

Benign

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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