rs327

Positions:

• chr8-19962025-T-G

Variant summary

Our verdict is Benign. Variant got -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:2
• Conservation: PhyloP100: 0.0580

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 1165815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19962025-T-G is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
LPL	NM_000237.3	c.1323-90T>G		intron_variant		ENST00000650287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPL	ENST00000650287.1	c.1323-90T>G		intron_variant			NM_000237.3	P1
LPL	ENST00000650478.1	c.*146-90T>G		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR exome AF: 0.402

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.276

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

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.295

Alfa AF: 0.285 Hom.: 11008

Bravo AF: 0.313

Asia WGS AF: 0.244 AC: 846 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	This variant is associated with the following publications: (PMID: 20650961) -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 12, 2024	- -

Computational scores

Source: dbNSFP v4.3

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

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: rs327; hg19: chr8-19819536;