8-19965319-G-C

Variant names:

• chr8-19965319-G-C
• rs4922115
• NM_000237.3:c.*9G>C

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.*9G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 628,166 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: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 0 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: 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=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	NM_000237.3	MANE Select	c.*9G>C		3_prime_UTR	Exon 10 of 10	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.*9G>C		3_prime_UTR	Exon 10 of 10	ENSP00000497642.1
	LPL	ENST00000650478.1		n.*260G>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000497560.1
	LPL	ENST00000650478.1		n.*260G>C		3_prime_UTR	Exon 4 of 4	ENSP00000497560.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 1 AN: 628166 Hom.: 0 Cov.: 0 AF XY: 0.00000292 AC XY: 1 AN XY: 342206

African (AFR) AF: 0.00 AC: 0 AN: 17672

American (AMR) AF: 0.00 AC: 0 AN: 43710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20958

East Asian (EAS) AF: 0.00 AC: 0 AN: 36036

South Asian (SAS) AF: 0.0000144 AC: 1 AN: 69674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 349808

Other (OTH) AF: 0.00 AC: 0 AN: 33084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4922115; hg19: chr8-19822830;