8-19939158-G-T

Position:

• chr8-19939158-G-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The ENST00000524029.5(LPL):​c.-153-130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 512,914 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (15 hom.)
• Consequence: LPL ENST00000524029.5 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 3.24

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 8-19939158-G-T is Benign according to our data. Variant chr8-19939158-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 362398.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr8-19939158-G-T is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.19939158G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000524029.5	c.-153-130G>T		intron_variant		4		ENSP00000428237.1
LPL	ENST00000520959.5	c.-140-9022G>T		intron_variant		4		ENSP00000428496.1
LPL	ENST00000522701.5	c.-218-65G>T		intron_variant		4		ENSP00000428557.1

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 1014 AN: 152062 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00395

Gnomad FIN AF: 0.00538

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.00758 AC: 2735 AN: 360734 Hom.: 15 Cov.: 0 AF XY: 0.00741 AC XY: 1396 AN XY: 188330

Gnomad4 AFR exome AF: 0.00268

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.00182

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00272

Gnomad4 FIN exome AF: 0.00681

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00667

GnomAD4 genome AF: 0.00666 AC: 1013 AN: 152180 Hom.: 9 Cov.: 32 AF XY: 0.00659 AC XY: 490 AN XY: 74378

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00374

Gnomad4 FIN AF: 0.00538

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00768 Hom.: 2

Bravo AF: 0.00593

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Hyperlipoproteinemia, type I Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 18, 2019	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.94

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: rs80351041; hg19: chr8-19796669;