NM_000237.3:c.249+820C>G

Variant names:

• chr8-19949160-C-G
• rs8176337
• NM_000237.3:c.249+820C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000237.3(LPL):​c.249+820C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 152,008 control chromosomes in the GnomAD database, including 11,210 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (11210 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.249+820C>G		intron_variant	Intron 2 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.249+820C>G		intron_variant	Intron 2 of 9		NM_000237.3	ENSP00000497642.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51018 AN: 151892 Hom.: 11174 Cov.: 32

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.336 AC: 51108 AN: 152008 Hom.: 11210 Cov.: 32 AF XY: 0.328 AC XY: 24402 AN XY: 74304

African (AFR) AF: 0.627 AC: 25974 AN: 41444

American (AMR) AF: 0.200 AC: 3046 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3470

East Asian (EAS) AF: 0.156 AC: 807 AN: 5172

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1765 AN: 10566

Middle Eastern (MID) AF: 0.267 AC: 77 AN: 288

European-Non Finnish (NFE) AF: 0.240 AC: 16332 AN: 67970

Other (OTH) AF: 0.294 AC: 619 AN: 2108

Alfa AF: 0.169 Hom.: 350

Bravo AF: 0.346

Asia WGS AF: 0.251 AC: 873 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.16
PhyloP100		-0.20

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: rs8176337; hg19: chr8-19806671;