rs4922115

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-19965319-G-A
• chr8-19965319-G-C

Variant summary

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

The NM_000237.3(LPL):​c.*9G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 779,480 control chromosomes in the GnomAD database, including 8,873 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 0.14 (1651 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7222 hom.)
• Consequence: LPL NM_000237.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0420
• Publications: 26 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.*9G>A		3_prime_UTR_variant	Exon 10 of 10		NM_000237.3	ENSP00000497642.1
LPL	ENST00000650478.1	n.*260G>A		non_coding_transcript_exon_variant	Exon 4 of 4			ENSP00000497560.1
LPL	ENST00000650478.1	n.*260G>A		3_prime_UTR_variant	Exon 4 of 4			ENSP00000497560.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21918 AN: 152030 Hom.: 1648 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0950

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.146 AC: 36519 AN: 250584 AF XY: 0.147

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.0951

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.147 AC: 92435 AN: 627332 Hom.: 7222 Cov.: 0 AF XY: 0.148 AC XY: 50474 AN XY: 341746

African (AFR) AF: 0.113 AC: 2001 AN: 17632

American (AMR) AF: 0.146 AC: 6372 AN: 43620

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 4898 AN: 20914

East Asian (EAS) AF: 0.0762 AC: 2743 AN: 36016

South Asian (SAS) AF: 0.132 AC: 9168 AN: 69524

European-Finnish (FIN) AF: 0.155 AC: 8209 AN: 53016

Middle Eastern (MID) AF: 0.171 AC: 709 AN: 4146

European-Non Finnish (NFE) AF: 0.153 AC: 53288 AN: 349410

Other (OTH) AF: 0.153 AC: 5047 AN: 33054

GnomAD4 genome AF: 0.144 AC: 21928 AN: 152148 Hom.: 1651 Cov.: 32 AF XY: 0.144 AC XY: 10701 AN XY: 74382

African (AFR) AF: 0.114 AC: 4716 AN: 41504

American (AMR) AF: 0.156 AC: 2380 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3472

East Asian (EAS) AF: 0.0950 AC: 492 AN: 5178

South Asian (SAS) AF: 0.126 AC: 606 AN: 4818

European-Finnish (FIN) AF: 0.156 AC: 1656 AN: 10584

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10710 AN: 67980

Other (OTH) AF: 0.145 AC: 307 AN: 2116

Alfa AF: 0.151 Hom.: 2582

Bravo AF: 0.143

Asia WGS AF: 0.123 AC: 428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 08, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The LPL c.*9G>A variant causes a missense change involving the alteration of a non-conserved nucleotide. One in silico tool predicts a benign outcome for this variant. The variant of interest has been found in a large, broad control population, ExAC in 17618/121272 control chromosomes at a frequency of 0.1452767, which is approximately 43 times the estimated maximal expected allele frequency of a pathogenic LPL variant (0.0033541), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as likely benign. Taken together, this variant is classified as benign. -

Oct 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hyperlipoproteinemia, type I Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dystrophin deficiency Benign:1

Sep 16, 2020

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	-0.90
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;