dbSNP rs17603420: LPIN1:c.1713+1158G>A (chr2-11789614-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001349206.2(LPIN1):c.1713+1158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,104 control chromosomes in the GnomAD database, including 21,930 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 0.51 ( 21930 hom., cov: 33)

Consequence

LPIN1
NM_001349206.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.877

Publications

3 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=-0.98).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2 link	c.1713+1158G>A		intron_variant	Intron 12 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.1713+1158G>A		intron_variant	Intron 12 of 20		NM_001349206.2	ENSP00000501331.1		Q14693-3

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

77945

AN:

151986

Hom.:

21891

Cov.:

show subpopulations

Gnomad AFR

AF:

0.749

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.373

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.443

Gnomad OTH

AF:

0.457

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

GnomAD4 genome

AF:

0.513

AC:

78034

AN:

152104

Hom.:

21930

Cov.:

AF XY:

0.507

AC XY:

37711

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.750

AC:

31122

AN:

41516

American (AMR)

AF:

0.389

AC:

5936

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.373

AC:

1296

AN:

3472

East Asian (EAS)

AF:

0.214

AC:

1110

AN:

5176

South Asian (SAS)

AF:

0.347

AC:

1669

AN:

4814

European-Finnish (FIN)

AF:

0.505

AC:

5344

AN:

10576

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.443

AC:

30118

AN:

67964

Other (OTH)

AF:

0.451

AC:

952

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1814

3628

5443

7257

9071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.479

Hom.:

30772

Bravo

AF:

0.514

Asia WGS

AF:

0.275

AC:

959

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.032

(source)

DANN

Benign

0.40

PhyloP100

-0.88

RBP_binding_hub_radar

0.85

RBP_regulation_power_radar

1.9

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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