rs270

Variant names:

• chr8-19956165-C-A
• rs270
• NM_000237.3:c.1018+82C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000237.3(LPL):​c.1018+82C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 1,573,220 control chromosomes in the GnomAD database, including 19,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1691 hom., cov: 33)
  • Exomes 𝑓: 0.16 (17801 hom.)
• Consequence: LPL NM_000237.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.526
• Publications: 27 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-19956165-C-A is Benign according to our data. Variant chr8-19956165-C-A is described in ClinVar as Benign. ClinVar VariationId is 1227345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.1018+82C>A		intron_variant	Intron 6 of 9	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.1018+82C>A		intron_variant	Intron 6 of 9		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.79+82C>A		intron_variant	Intron 1 of 3			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21543 AN: 152102 Hom.: 1692 Cov.: 33

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.156 AC: 221079 AN: 1421000 Hom.: 17801 AF XY: 0.154 AC XY: 109491 AN XY: 709014

African (AFR) AF: 0.0879 AC: 2871 AN: 32658

American (AMR) AF: 0.167 AC: 7423 AN: 44508

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2826 AN: 25870

East Asian (EAS) AF: 0.0984 AC: 3887 AN: 39500

South Asian (SAS) AF: 0.125 AC: 10561 AN: 84814

European-Finnish (FIN) AF: 0.229 AC: 10977 AN: 47968

Middle Eastern (MID) AF: 0.0915 AC: 473 AN: 5170

European-Non Finnish (NFE) AF: 0.161 AC: 173625 AN: 1081364

Other (OTH) AF: 0.143 AC: 8436 AN: 59148

GnomAD4 genome AF: 0.142 AC: 21552 AN: 152220 Hom.: 1691 Cov.: 33 AF XY: 0.143 AC XY: 10611 AN XY: 74406

African (AFR) AF: 0.0913 AC: 3796 AN: 41558

American (AMR) AF: 0.160 AC: 2445 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 359 AN: 3472

East Asian (EAS) AF: 0.124 AC: 642 AN: 5176

South Asian (SAS) AF: 0.120 AC: 576 AN: 4816

European-Finnish (FIN) AF: 0.229 AC: 2420 AN: 10586

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10864 AN: 68000

Other (OTH) AF: 0.134 AC: 284 AN: 2116

Alfa AF: 0.151 Hom.: 3104

Bravo AF: 0.135

Asia WGS AF: 0.104 AC: 364 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperlipoproteinemia, type I Benign:1

Aug 28, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.1
DANN	Benign	0.67
PhyloP100		0.53

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: rs270; hg19: chr8-19813676;