Variant rs142083008 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_001349206.2(LPIN1):c.1644-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,528,396 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

LPIN1
NM_001349206.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.75

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:

LPIN1 (HGNC:):

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 2-11788351-C-T is Benign according to our data. Variant chr2-11788351-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262584.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 = 0.0041 (624/152242) while in subpopulation AFR AF= 0.0103 (426/41532). AF 95% confidence interval is 0.00945. There are 2 homozygotes in gnomad4. There are 282 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001349206.2 linkuse as main transcript	c.1644-36C>T		intron_variant		ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1 linkuse as main transcript	c.1644-36C>T		intron_variant			NM_001349206.2	ENSP00000501331.1		Q14693-3

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

617

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00200

AC:

502

AN:

251272

Hom.:

AF XY:

0.00190

AC XY:

258

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0108

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00129

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00122

AC:

1673

AN:

1376154

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

838

AN XY:

689938

show subpopulations

Gnomad4 AFR exome

AF:

0.00981

Gnomad4 AMR exome

AF:

0.00193

Gnomad4 ASJ exome

AF:

0.00934

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000296

Gnomad4 FIN exome

AF:

0.0000938

Gnomad4 NFE exome

AF:

0.000823

Gnomad4 OTH exome

AF:

0.00244

GnomAD4 genome

AF:

0.00410

AC:

624

AN:

152242

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00280

Hom.:

Bravo

AF:

0.00497

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.055

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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