rs326

Positions:

• chr8-19961928-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.1323-187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 151,996 control chromosomes in the GnomAD database, including 11,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11436 hom., cov: 31)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.152

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-19961928-A-G is Benign according to our data. Variant chr8-19961928-A-G is described in ClinVar as [Benign]. Clinvar id is 1559.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-19961928-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPL	NM_000237.3	c.1323-187A>G		intron_variant		ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1323-187A>G		intron_variant			NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*146-187A>G		intron_variant				ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55740 AN: 151880 Hom.: 11404 Cov.: 31

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.367 AC: 55815 AN: 151996 Hom.: 11436 Cov.: 31 AF XY: 0.362 AC XY: 26871 AN XY: 74308

Gnomad4 AFR AF: 0.556

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.346

Alfa AF: 0.311 Hom.: 9229

Bravo AF: 0.379

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 08, 2019

- -

High density lipoprotein cholesterol level quantitative trait locus 11 Other:1

association, no assertion criteria provided

literature only

OMIM

Jan 10, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.48

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: rs326; hg19: chr8-19819439;