NM_000237.3:c.1428-1006T>G

Variant names:

• chr8-19964304-T-G
• rs10099160
• NM_000237.3:c.1428-1006T>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.1428-1006T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,122 control chromosomes in the GnomAD database, including 3,247 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 0.19 (3247 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 21 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1428-1006T>G		intron_variant	Intron 9 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1428-1006T>G		intron_variant	Intron 9 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*251-1006T>G		intron_variant	Intron 3 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29501 AN: 152002 Hom.: 3251 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.194 AC: 29498 AN: 152122 Hom.: 3247 Cov.: 32 AF XY: 0.194 AC XY: 14422 AN XY: 74348

African (AFR) AF: 0.114 AC: 4734 AN: 41530

American (AMR) AF: 0.188 AC: 2875 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.135 AC: 696 AN: 5162

South Asian (SAS) AF: 0.145 AC: 701 AN: 4822

European-Finnish (FIN) AF: 0.304 AC: 3215 AN: 10560

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16200 AN: 67990

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.219 Hom.: 2121

Bravo AF: 0.184

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		0.063

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: rs10099160; hg19: chr8-19821815;