Variant chr2-11713862-A-T 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+50A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 1,292,316 control chromosomes in the GnomAD database, including 170,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14148 hom., cov: 33)

Exomes 𝑓: 0.52 ( 156659 hom. )

Consequence

LPIN1
NM_001261428.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0360

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=-0.9).

BP6

Variant 2-11713862-A-T is Benign according to our data. Variant chr2-11713862-A-T is described in ClinVar as [Benign]. Clinvar id is 683084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
LPIN1	NM_001261428.3 link	c.138+50A>T	intron_variant	Intron 2 of 21	NP_001248357.1	Q14693-7
LPIN1	NM_001349207.2 link	c.81+36134A>T	intron_variant	Intron 1 of 20	NP_001336136.1
LPIN1	NM_001349208.2 link	c.138+50A>T	intron_variant	Intron 2 of 20	NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6 link	c.138+50A>T		intron_variant	Intron 2 of 21	2		ENSP00000397908.2		Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60323

AN:

152042

Hom.:

14147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.439

GnomAD3 exomes

AF:

0.494

AC:

60640

AN:

122656

Hom.:

15538

AF XY:

0.504

AC XY:

33783

AN XY:

67052

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.523

Gnomad ASJ exome

AF:

0.540

Gnomad EAS exome

AF:

0.421

Gnomad SAS exome

AF:

0.569

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.505

Gnomad OTH exome

AF:

0.491

GnomAD4 exome

AF:

0.522

AC:

594804

AN:

1140156

Hom.:

156659

Cov.:

AF XY:

0.524

AC XY:

299669

AN XY:

572216

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.434

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.537

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.396

AC:

60330

AN:

152160

Hom.:

14148

Cov.:

AF XY:

0.400

AC XY:

29718

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.133

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.492

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.451

Hom.:

3077

Bravo

AF:

0.380

Asia WGS

AF:

0.505

AC:

1757

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.4

DANN

Benign

0.72

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