rs326

Variant names:

• chr8-19961928-A-G
• rs326
• NM_000237.3:c.1323-187A>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.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
• Publications: 93 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=-0.92).
• BP6: Variant 8-19961928-A-G is Benign according to our data. Variant chr8-19961928-A-G is described in ClinVar as Benign. ClinVar VariationId is 1559.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1323-187A>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.1323-187A>G		intron_variant	Intron 8 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*146-187A>G		intron_variant	Intron 2 of 3			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

African (AFR) AF: 0.556 AC: 23033 AN: 41426

American (AMR) AF: 0.308 AC: 4706 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3464

East Asian (EAS) AF: 0.206 AC: 1061 AN: 5154

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2756 AN: 10578

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20328 AN: 67970

Other (OTH) AF: 0.346 AC: 730 AN: 2112

Alfa AF: 0.318 Hom.: 26420

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

Apr 08, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Jan 10, 2013

OMIM

Significance: association

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.48
PhyloP100		-0.15

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: rs326; hg19: chr8-19819439;