Variant 2-11713837-C-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+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,458,688 control chromosomes in the GnomAD database, including 7,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.074 ( 561 hom., cov: 33)

Exomes 𝑓: 0.096 ( 6832 hom. )

Consequence

LPIN1
NM_001261428.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.826

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=-0.88).

BP6

Variant 2-11713837-C-T is Benign according to our data. Variant chr2-11713837-C-T is described in ClinVar as [Benign]. Clinvar id is 1270822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
LPIN1	NM_001261428.3 linkuse as main transcript	c.138+25C>T	intron_variant	NP_001248357.1
LPIN1	NM_001349207.2 linkuse as main transcript	c.81+36109C>T	intron_variant	NP_001336136.1
LPIN1	NM_001349208.2 linkuse as main transcript	c.138+25C>T	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+25C>T		intron_variant		2		ENSP00000397908	A2	Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.0742

AC:

11281

AN:

152098

Hom.:

564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.0585

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0856

GnomAD3 exomes

AF:

0.0723

AC:

8865

AN:

122548

Hom.:

408

AF XY:

0.0723

AC XY:

4837

AN XY:

66888

show subpopulations

Gnomad AFR exome

AF:

0.0187

Gnomad AMR exome

AF:

0.0441

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.000196

Gnomad SAS exome

AF:

0.0374

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.0880

GnomAD4 exome

AF:

0.0963

AC:

125755

AN:

1306472

Hom.:

6832

Cov.:

AF XY:

0.0954

AC XY:

61762

AN XY:

647680

show subpopulations

Gnomad4 AFR exome

AF:

0.0146

Gnomad4 AMR exome

AF:

0.0457

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.000169

Gnomad4 SAS exome

AF:

0.0377

Gnomad4 FIN exome

AF:

0.0982

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0882

GnomAD4 genome

AF:

0.0741

AC:

11272

AN:

152216

Hom.:

561

Cov.:

AF XY:

0.0731

AC XY:

5438

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0193

Gnomad4 AMR

AF:

0.0584

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.0315

Gnomad4 FIN

AF:

0.0949

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0848

Alfa

AF:

0.105

Hom.:

250

Bravo

AF:

0.0697

Asia WGS

AF:

0.0150

AC:

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

DANN

Benign

0.66

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