rs4669769

Positions:

chr2-11677686-G-C

Variant summary

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

The NM_001261428.3(LPIN1):c.39G>C(p.Glu13Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,535,318 control chromosomes in the GnomAD database, including 315,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 24959 hom., cov: 33)

Exomes 𝑓: 0.64 ( 290103 hom. )

Consequence

LPIN1
NM_001261428.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.349

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=2.3455743E-6).

BP6

Variant 2-11677686-G-C is Benign according to our data. Variant chr2-11677686-G-C is described in ClinVar as [Benign]. Clinvar id is 403044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein
LPIN1	NM_001261428.3 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	1/22	NP_001248357.1
LPIN1	NM_001349207.2 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	1/21	NP_001336136.1
LPIN1	NM_001349208.2 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	1/21	NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6 linkuse as main transcript	c.39G>C	p.Glu13Asp	missense_variant	1/22	2		ENSP00000397908	A2	Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84307

AN:

152048

Hom.:

24969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.808

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.390

Gnomad SAS

AF:

0.661

Gnomad FIN

AF:

0.615

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.565

GnomAD3 exomes

AF:

0.606

AC:

77797

AN:

128392

Hom.:

24214

AF XY:

0.613

AC XY:

43095

AN XY:

70310

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.626

Gnomad ASJ exome

AF:

0.599

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.654

Gnomad FIN exome

AF:

0.629

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.603

GnomAD4 exome

AF:

0.644

AC:

890257

AN:

1383152

Hom.:

290103

Cov.:

AF XY:

0.645

AC XY:

440311

AN XY:

682504

show subpopulations

Gnomad4 AFR exome

AF:

0.330

Gnomad4 AMR exome

AF:

0.615

Gnomad4 ASJ exome

AF:

0.597

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.659

Gnomad4 FIN exome

AF:

0.619

Gnomad4 NFE exome

AF:

0.664

Gnomad4 OTH exome

AF:

0.614

GnomAD4 genome

AF:

0.554

AC:

84321

AN:

152166

Hom.:

24959

Cov.:

AF XY:

0.554

AC XY:

41180

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.345

Gnomad4 AMR

AF:

0.609

Gnomad4 ASJ

AF:

0.607

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.660

Gnomad4 FIN

AF:

0.615

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.604

Hom.:

5242

Bravo

AF:

0.538

TwinsUK

AF:

0.649

AC:

2406

ALSPAC

AF:

0.662

AC:

2550

ExAC

AF:

0.562

AC:

8620

Asia WGS

AF:

0.546

AC:

1896

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Myoglobinuria, acute recurrent, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

3.5

DANN

Uncertain

0.99

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.040

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Vest4

0.049

MutPred

0.10

Gain of sheet (P = 0.0827);

MPC

0.16

ClinPred

0.0090

GERP RS

-0.51

gMVP

0.069

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