8-19962025-T-G

Variant names:

• chr8-19962025-T-G
• rs327
• NM_000237.3:c.1323-90T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):​c.1323-90T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 854,874 control chromosomes in the GnomAD database, including 33,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7580 hom., cov: 32)
  • Exomes 𝑓: 0.26 (25645 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0580
• Publications: 48 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 8-19962025-T-G is Benign according to our data. Variant chr8-19962025-T-G is described in ClinVar as Benign. ClinVar VariationId is 1165815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1323-90T>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.1323-90T>G		intron_variant	Intron 8 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*146-90T>G		intron_variant	Intron 2 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46886 AN: 152014 Hom.: 7567 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.294

GnomAD4 exome AF: 0.265 AC: 186188 AN: 702742 Hom.: 25645 AF XY: 0.264 AC XY: 99765 AN XY: 377628

African (AFR) AF: 0.402 AC: 7633 AN: 18976

American (AMR) AF: 0.225 AC: 9715 AN: 43156

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 8162 AN: 20914

East Asian (EAS) AF: 0.201 AC: 7096 AN: 35384

South Asian (SAS) AF: 0.230 AC: 16216 AN: 70584

European-Finnish (FIN) AF: 0.248 AC: 12162 AN: 49120

Middle Eastern (MID) AF: 0.296 AC: 1263 AN: 4270

European-Non Finnish (NFE) AF: 0.269 AC: 114318 AN: 425514

Other (OTH) AF: 0.276 AC: 9623 AN: 34824

GnomAD4 genome AF: 0.308 AC: 46924 AN: 152132 Hom.: 7580 Cov.: 32 AF XY: 0.305 AC XY: 22686 AN XY: 74382

African (AFR) AF: 0.402 AC: 16686 AN: 41468

American (AMR) AF: 0.269 AC: 4107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1079 AN: 5182

South Asian (SAS) AF: 0.226 AC: 1091 AN: 4826

European-Finnish (FIN) AF: 0.251 AC: 2658 AN: 10604

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18920 AN: 67970

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.291 Hom.: 18367

Bravo AF: 0.313

Asia WGS AF: 0.244 AC: 846 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20650961) -

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.75
PhyloP100		0.058

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: rs327; hg19: chr8-19819536;