rs331

Variant names:

• chr8-19962894-G-A
• rs331
• NM_000237.3:c.1427+675G>A

Variant summary

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

The NM_000237.3(LPL):​c.1427+675G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,114 control chromosomes in the GnomAD database, including 6,902 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 0.29 (6902 hom., cov: 33)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.745
• Publications: 53 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1427+675G>A		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.1427+675G>A		intron_variant	Intron 9 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*250+675G>A		intron_variant	Intron 3 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44817 AN: 151996 Hom.: 6893 Cov.: 33

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.295 AC: 44846 AN: 152114 Hom.: 6902 Cov.: 33 AF XY: 0.291 AC XY: 21668 AN XY: 74370

African (AFR) AF: 0.376 AC: 15615 AN: 41506

American (AMR) AF: 0.257 AC: 3928 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5176

South Asian (SAS) AF: 0.225 AC: 1088 AN: 4830

European-Finnish (FIN) AF: 0.249 AC: 2628 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 78 AN: 290

European-Non Finnish (NFE) AF: 0.268 AC: 18205 AN: 67974

Other (OTH) AF: 0.283 AC: 597 AN: 2110

Alfa AF: 0.276 Hom.: 11851

Bravo AF: 0.299

Asia WGS AF: 0.240 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.7
DANN	Benign	0.67
PhyloP100		0.74

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: rs331; hg19: chr8-19820405;