rs45509591

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001349206.2(LPIN1):c.193-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,253,424 control chromosomes in the GnomAD database, including 20,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1858 hom., cov: 32)

Exomes 𝑓: 0.18 ( 19037 hom. )

Consequence

LPIN1
NM_001349206.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.65

Publications

5 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 links:

MIR548S (HGNC:38354): (microRNA 548s) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR548S links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 2-11767716-C-T is Benign according to our data. Variant chr2-11767716-C-T is described in ClinVar as Benign. ClinVar VariationId is 262589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349206.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPIN1	NM_001349206.2	MANE Select	c.193-47C>T	intron	N/A	NP_001336135.1	Q14693-3
LPIN1	NM_001261428.3		c.340-47C>T	intron	N/A	NP_001248357.1	Q14693-7
LPIN1	NM_001349207.2		c.283-47C>T	intron	N/A	NP_001336136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LPIN1	ENST00000674199.1	MANE Select	c.193-47C>T	intron	N/A	ENSP00000501331.1	Q14693-3
LPIN1	ENST00000256720.6	TSL:1	c.193-47C>T	intron	N/A	ENSP00000256720.2	Q14693-1
LPIN1	ENST00000396098.5	TSL:1	c.211-47C>T	intron	N/A	ENSP00000379405.1	Q14693-6

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21920

AN:

151994

Hom.:

1861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0747

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.00347

Gnomad SAS

AF:

0.101

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.217

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.143

AC:

35887

AN:

250136

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.0752

Gnomad AMR exome

AF:

0.0732

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.00371

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.158

GnomAD4 exome

AF:

0.176

AC:

194206

AN:

1101312

Hom.:

19037

Cov.:

AF XY:

0.176

AC XY:

99497

AN XY:

565536

show subpopulations

African (AFR)

AF:

0.0721

AC:

1910

AN:

26498

American (AMR)

AF:

0.0785

AC:

3471

AN:

44242

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

4636

AN:

23978

East Asian (EAS)

AF:

0.00294

AC:

112

AN:

38040

South Asian (SAS)

AF:

0.108

AC:

8540

AN:

79032

European-Finnish (FIN)

AF:

0.166

AC:

8818

AN:

53246

Middle Eastern (MID)

AF:

0.155

AC:

788

AN:

5082

European-Non Finnish (NFE)

AF:

0.202

AC:

157996

AN:

782714

Other (OTH)

AF:

0.164

AC:

7935

AN:

48480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

8634

17268

25902

34536

43170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4448

8896

13344

17792

22240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.144

AC:

21925

AN:

152112

Hom.:

1858

Cov.:

AF XY:

0.141

AC XY:

10511

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0748

AC:

3106

AN:

41504

American (AMR)

AF:

0.109

AC:

1672

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.195

AC:

677

AN:

3464

East Asian (EAS)

AF:

0.00367

AC:

AN:

5178

South Asian (SAS)

AF:

0.101

AC:

485

AN:

4816

European-Finnish (FIN)

AF:

0.171

AC:

1808

AN:

10552

Middle Eastern (MID)

AF:

0.202

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.200

AC:

13620

AN:

67998

Other (OTH)

AF:

0.144

AC:

303

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

931

1862

2794

3725

4656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.152

Hom.:

1501

Bravo

AF:

0.136

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.030

(source)

DANN

Benign

0.42

PhyloP100

-1.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over