8-19939370-C-T

Variant names:

• chr8-19939370-C-T
• rs559590399
• NM_000237.3:c.-71C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000237.3(LPL):​c.-71C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,336,350 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: LPL NM_000237.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881
• Publications: 1 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Laboratory for Molecular Medicine, Ambry Genetics
• hyperlipidemia, familial combined, LPL related

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000237.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.-71C>T		5_prime_UTR	Exon 1 of 10	NP_000228.1	P06858

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.-71C>T		5_prime_UTR	Exon 1 of 10	ENSP00000497642.1	P06858
	LPL	ENST00000965928.1		c.-71C>T		5_prime_UTR	Exon 3 of 12	ENSP00000635987.1
	LPL	ENST00000965929.1		c.-71C>T		5_prime_UTR	Exon 1 of 10	ENSP00000635988.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000150 AC: 2 AN: 1336350 Hom.: 0 Cov.: 24 AF XY: 0.00000302 AC XY: 2 AN XY: 662930

African (AFR) AF: 0.00 AC: 0 AN: 30718

American (AMR) AF: 0.00 AC: 0 AN: 35746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24746

East Asian (EAS) AF: 0.00 AC: 0 AN: 35950

South Asian (SAS) AF: 0.00 AC: 0 AN: 78250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1025072

Other (OTH) AF: 0.00 AC: 0 AN: 55886

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.0
DANN	Benign	0.80
PhyloP100		-0.88
PromoterAI		-0.017	Neutral

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: rs559590399; hg19: chr8-19796881;