Variant chr2-11713717-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_StrongBS1BS2

The NM_001261428.3(LPIN1):c.82-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,251,100 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 36 hom., cov: 33)

Exomes 𝑓: 0.012 ( 156 hom. )

Consequence

LPIN1
NM_001261428.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0150

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=-0.81).

BP6

Variant 2-11713717-C-T is Benign according to our data. Variant chr2-11713717-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1193983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0187 (2845/152256) while in subpopulation AFR AF= 0.0384 (1595/41544). AF 95% confidence interval is 0.0368. There are 36 homozygotes in gnomad4. There are 1421 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
LPIN1	NM_001261428.3 linkuse as main transcript	c.82-39C>T	intron_variant	NP_001248357.1
LPIN1	NM_001349207.2 linkuse as main transcript	c.81+35989C>T	intron_variant	NP_001336136.1
LPIN1	NM_001349208.2 linkuse as main transcript	c.82-39C>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.82-39C>T		intron_variant		2		ENSP00000397908	A2	Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2847

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0150

AC:

1801

AN:

119892

Hom.:

AF XY:

0.0160

AC XY:

1046

AN XY:

65448

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.00973

Gnomad ASJ exome

AF:

0.00958

Gnomad EAS exome

AF:

0.000986

Gnomad SAS exome

AF:

0.0322

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0119

AC:

13048

AN:

1098844

Hom.:

156

Cov.:

AF XY:

0.0125

AC XY:

6901

AN XY:

553182

show subpopulations

Gnomad4 AFR exome

AF:

0.0379

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.00996

Gnomad4 EAS exome

AF:

0.000521

Gnomad4 SAS exome

AF:

0.0316

Gnomad4 FIN exome

AF:

0.00890

Gnomad4 NFE exome

AF:

0.00970

Gnomad4 OTH exome

AF:

0.0155

GnomAD4 genome

AF:

0.0187

AC:

2845

AN:

152256

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1421

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0384

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0330

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.0132

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Likely 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

-0.81

CADD

Benign

5.9

DANN

Benign

0.68

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