Variant chr2-11713838-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001261428.3(LPIN1):c.138+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,434,026 control chromosomes in the GnomAD database, including 32,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3223 hom., cov: 33)

Exomes 𝑓: 0.21 ( 29710 hom. )

Consequence

LPIN1
NM_001261428.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.134

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-11713838-G-A is Benign according to our data. Variant chr2-11713838-G-A is described in ClinVar as [Benign]. Clinvar id is 683087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
LPIN1	NM_001261428.3 linkuse as main transcript	c.138+26G>A	intron_variant	NP_001248357.1
LPIN1	NM_001349207.2 linkuse as main transcript	c.81+36110G>A	intron_variant	NP_001336136.1
LPIN1	NM_001349208.2 linkuse as main transcript	c.138+26G>A	intron_variant	NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6 linkuse as main transcript	c.138+26G>A		intron_variant		2		ENSP00000397908	A2	Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27566

AN:

152078

Hom.:

3220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0432

Gnomad AMI

AF:

0.268

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.224

AC:

27625

AN:

123200

Hom.:

3422

AF XY:

0.226

AC XY:

15228

AN XY:

67296

show subpopulations

Gnomad AFR exome

AF:

0.0382

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.252

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.212

AC:

271860

AN:

1281830

Hom.:

29710

Cov.:

AF XY:

0.214

AC XY:

136510

AN XY:

636512

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.192

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.212

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.181

AC:

27565

AN:

152196

Hom.:

3223

Cov.:

AF XY:

0.185

AC XY:

13764

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0430

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.207

Gnomad4 EAS

AF:

0.171

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.275

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.244

Hom.:

6002

Bravo

AF:

0.172

Asia WGS

AF:

0.172

AC:

599

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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. -

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_noAF

Benign

-0.82

CADD

Benign

6.7

DANN

Benign

0.63

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