NM_000237.3:c.776-172G>A

Variant names:

• chr8-19955669-G-A
• rs264
• NM_000237.3:c.776-172G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000237.3(LPL):​c.776-172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,956 control chromosomes in the GnomAD database, including 1,653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1653 hom., cov: 32)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0340
• Publications: 98 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-19955669-G-A is Benign according to our data. Variant chr8-19955669-G-A is described in ClinVar as Benign. ClinVar VariationId is 1282596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

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.776-172G>A		intron	N/A	NP_000228.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPL	ENST00000650287.1	MANE Select	c.776-172G>A		intron	N/A	ENSP00000497642.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21595 AN: 151838 Hom.: 1648 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.142 AC: 21597 AN: 151956 Hom.: 1653 Cov.: 32 AF XY: 0.143 AC XY: 10589 AN XY: 74284

African (AFR) AF: 0.127 AC: 5254 AN: 41446

American (AMR) AF: 0.159 AC: 2432 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1086 AN: 5166

South Asian (SAS) AF: 0.183 AC: 875 AN: 4790

European-Finnish (FIN) AF: 0.102 AC: 1082 AN: 10560

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.143 AC: 9705 AN: 67952

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.144 Hom.: 5446

Bravo AF: 0.143

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		-0.034

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: rs264; hg19: chr8-19813180;