2-11713787-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001261428.3(LPIN1):c.113G>A(p.Arg38Gln) variant causes a missense change. The variant allele was found at a frequency of 0.219 in 1,505,294 control chromosomes in the GnomAD database, including 38,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3224 hom., cov: 33)

Exomes 𝑓: 0.22 ( 35594 hom. )

Consequence

LPIN1
NM_001261428.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:4

Conservation

PhyloP100: 4.11

Variant links:

Genes affected

LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]

LPIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019290447).

BP6

Variant 2-11713787-G-A is Benign according to our data. Variant chr2-11713787-G-A is described in ClinVar as [Benign]. Clinvar id is 403045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
LPIN1	NM_001261428.3 link	c.113G>A	p.Arg38Gln	missense_variant	Exon 2 of 22	NP_001248357.1	Q14693-7
LPIN1	NM_001349208.2 link	c.113G>A	p.Arg38Gln	missense_variant	Exon 2 of 21	NP_001336137.1
LPIN1	NM_001349207.2 link	c.81+36059G>A		intron_variant	Intron 1 of 20	NP_001336136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6 link	c.113G>A	p.Arg38Gln	missense_variant	Exon 2 of 22	2		ENSP00000397908.2		Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27583

AN:

152004

Hom.:

3221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.227

AC:

28792

AN:

126740

Hom.:

3632

AF XY:

0.229

AC XY:

15874

AN XY:

69360

show subpopulations

Gnomad AFR exome

AF:

0.0383

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.153

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.223

AC:

301780

AN:

1353172

Hom.:

35594

Cov.:

AF XY:

0.225

AC XY:

150184

AN XY:

668858

show subpopulations

Gnomad4 AFR exome

AF:

0.0361

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.195

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.181

AC:

27582

AN:

152122

Hom.:

3224

Cov.:

AF XY:

0.185

AC XY:

13775

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.206

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.222

Hom.:

4075

Bravo

AF:

0.172

TwinsUK

AF:

0.231

AC:

856

ALSPAC

AF:

0.220

AC:

846

ExAC

AF:

0.209

AC:

2860

Asia WGS

AF:

0.173

AC:

600

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hyperchloremia

Pathogenic:1

Phenosystems SA

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: 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: Frequency -

LPIN1-related disorder

Benign:1

Apr 02, 2020

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.10

REVEL

Uncertain

0.32

Sift

Benign

0.11

Sift4G

Pathogenic

0.0

Vest4

0.15

MPC

0.22

ClinPred

0.016

GERP RS

4.9

gMVP

0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over