rs1801177

Variant names:

• chr8-19948197-G-A
• rs1801177
• NM_000237.3:c.106G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-19948197-G-A
• chr8-19948197-G-C
• chr8-19948197-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000237.3(LPL):​c.106G>A​(p.Asp36Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,613,866 control chromosomes in the GnomAD database, including 327 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,other (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (61 hom., cov: 31)
  • Exomes 𝑓: 0.016 (266 hom.)
• Consequence: LPL NM_000237.3 missense
• Clinical Significance: Benign/Likely benign; other criteria provided, multiple submitters, no conflicts P:1 B:11 O:3
• Conservation: PhyloP100: 3.48

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0077874362).
• BP6: Variant 8-19948197-G-A is Benign according to our data. Variant chr8-19948197-G-A is described in ClinVar as [Likely_benign, other]. Clinvar id is 1552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-19948197-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0222 (3374/152068) while in subpopulation AFR AF= 0.0458 (1900/41482). AF 95% confidence interval is 0.0441. There are 61 homozygotes in gnomad4. There are 1562 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPL	NM_000237.3	c.106G>A	p.Asp36Asn	missense_variant	Exon 2 of 10	ENST00000650287.1	NP_000228.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPL	ENST00000650287.1	c.106G>A	p.Asp36Asn	missense_variant	Exon 2 of 10		NM_000237.3	ENSP00000497642.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3377 AN: 151950 Hom.: 61 Cov.: 31

Gnomad AFR AF: 0.0459

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00190

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0141 AC: 3554 AN: 251484 Hom.: 45 AF XY: 0.0146 AC XY: 1987 AN XY: 135916

Gnomad AFR exome AF: 0.0466

Gnomad AMR exome AF: 0.00867

Gnomad ASJ exome AF: 0.00625

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0134

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.0167

Gnomad OTH exome AF: 0.0145

GnomAD4 exome AF: 0.0160 AC: 23441 AN: 1461798 Hom.: 266 Cov.: 31 AF XY: 0.0160 AC XY: 11635 AN XY: 727214

Gnomad4 AFR exome AF: 0.0489

Gnomad4 AMR exome AF: 0.00955

Gnomad4 ASJ exome AF: 0.00624

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.00212

Gnomad4 NFE exome AF: 0.0170

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0222 AC: 3374 AN: 152068 Hom.: 61 Cov.: 31 AF XY: 0.0210 AC XY: 1562 AN XY: 74338

Gnomad4 AFR AF: 0.0458

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0123

Gnomad4 FIN AF: 0.00190

Gnomad4 NFE AF: 0.0159

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0161 Hom.: 44

Bravo AF: 0.0246

TwinsUK AF: 0.0210 AC: 78

ALSPAC AF: 0.0205 AC: 79

ESP6500AA AF: 0.0454 AC: 200

ESP6500EA AF: 0.0177 AC: 152

ExAC AF: 0.0149 AC: 1811

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.0165

EpiControl AF: 0.0218

ClinVar

Significance: Benign/Likely benign; other

Submissions summary: Pathogenic:1 Benign:11 Other:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:1 Benign:3 Other:1

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 13, 2018

Eurofins Ntd Llc (ga)

Significance: other

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 11260209, 8839720, 15049943, 9678774, 28267856, 8872057, 10517255, 8541837, 8199176, 7749858, 26934567, 27055971, 24503134, 24123366, 21146168, 18823627, 12535736, 18922999, 28008009, 10364086) -

Hyperlipoproteinemia, type I Benign:4

Jan 02, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 06, 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. -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency, association with hyperlipidemia. -

Dec 10, 2021

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Mar 21, 2019

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

LPL-related disorder Benign:1

Sep 25, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Coronary heart disease Other:1

Sep 15, 2014

Blueprint Genetics

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hyperlipidemia, familial combined, susceptibility to Other:1

Aug 01, 1999

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	T;.;D;D
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D;D;.;D
MetaRNN	Benign	0.0078	T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.1	.;.;M;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N;.
REVEL	Uncertain	0.33
Sift	Benign	0.063	T;T;T;.
Sift4G	Uncertain	0.058	T;T;T;.
Polyphen		0.074	.;.;B;B
Vest4		0.055
MPC		0.089
ClinPred		0.022	T
GERP RS		4.3
Varity_R		0.24
gMVP		0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801177; hg19: chr8-19805708; COSMIC: COSV60931007;