8-19961566-T-G

Variant names:

• chr8-19961566-T-G
• rs320
• NM_000237.3:c.1322+483T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.1322+483T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,060 control chromosomes in the GnomAD database, including 6,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6080 hom., cov: 31)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.172
• Publications: 89 publications found

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 Gene-Disease associations (from GenCC):

• familial lipoprotein lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 8-19961566-T-G is Benign according to our data. Variant chr8-19961566-T-G is described in ClinVar as Benign. ClinVar VariationId is 1165812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1322+483T>G		intron_variant	Intron 8 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1322+483T>G		intron_variant	Intron 8 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*145+483T>G		intron_variant	Intron 2 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42808 AN: 151942 Hom.: 6073 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.282 AC: 42827 AN: 152060 Hom.: 6080 Cov.: 31 AF XY: 0.278 AC XY: 20682 AN XY: 74340

African (AFR) AF: 0.317 AC: 13125 AN: 41428

American (AMR) AF: 0.259 AC: 3960 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1073 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2648 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.274 AC: 18617 AN: 67986

Other (OTH) AF: 0.273 AC: 575 AN: 2110

Alfa AF: 0.271 Hom.: 9568

Bravo AF: 0.284

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs320; hg19: chr8-19819077;