Genetic Variant LPIN1:c.1807-778C>T (chr2-11794630-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001349206.2(LPIN1):c.1807-778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 138,614 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 33 hom., cov: 33)

Consequence

LPIN1
NM_001349206.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0170

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

myoglobinuria, acute recurrent, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
hereditary recurrent myoglobinuria
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LPIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.013 (1807/138614) while in subpopulation SAS AF = 0.0473 (211/4460). AF 95% confidence interval is 0.0421. There are 33 homozygotes in GnomAd4. There are 883 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 33 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2 link	c.1807-778C>T		intron_variant	Intron 13 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1 link	c.1807-778C>T		intron_variant	Intron 13 of 20		NM_001349206.2	ENSP00000501331.1		Q14693-3

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1807

AN:

138494

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00286

Gnomad AMI

AF:

0.0683

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0312

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.00213

Gnomad MID

AF:

0.0458

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0130

AC:

1807

AN:

138614

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

883

AN XY:

67568

show subpopulations

African (AFR)

AF:

0.00285

AC:

102

AN:

35826

American (AMR)

AF:

0.0143

AC:

206

AN:

14386

Ashkenazi Jewish (ASJ)

AF:

0.0312

AC:

104

AN:

3332

East Asian (EAS)

AF:

0.00117

AC:

AN:

5140

South Asian (SAS)

AF:

0.0473

AC:

211

AN:

4460

European-Finnish (FIN)

AF:

0.00213

AC:

AN:

9374

Middle Eastern (MID)

AF:

0.0458

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0167

AC:

1051

AN:

62986

Other (OTH)

AF:

0.0186

AC:

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

186

278

371

464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.7

(source)

DANN

Benign

0.82

PhyloP100

-0.017

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over