NM_001349206.2:c.1806+41G>T

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.1806+41G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,561,184 control chromosomes in the GnomAD database, including 289,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34288 hom., cov: 31)

Exomes 𝑓: 0.59 ( 255319 hom. )

Consequence

LPIN1
NM_001349206.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.583

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 2-11792047-G-T is Benign according to our data. Variant chr2-11792047-G-T is described in ClinVar as [Benign]. Clinvar id is 262586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2 link	c.1806+41G>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.1806+41G>T		intron_variant	Intron 13 of 20		NM_001349206.2	ENSP00000501331.1		Q14693-3

Frequencies

GnomAD3 genomes

AF:

0.650

AC:

98665

AN:

151824

Hom.:

34235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.580

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.517

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.606

Gnomad OTH

AF:

0.589

GnomAD2 exomes

AF:

0.539

AC:

130096

AN:

241264

AF XY:

0.537

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.361

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.619

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.545

GnomAD4 exome

AF:

0.593

AC:

835110

AN:

1409238

Hom.:

255319

Cov.:

AF XY:

0.587

AC XY:

412756

AN XY:

703174

show subpopulations

African (AFR)

AF:

0.901

AC:

29382

AN:

32618

American (AMR)

AF:

0.375

AC:

16276

AN:

43382

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

13180

AN:

25576

East Asian (EAS)

AF:

0.236

AC:

9229

AN:

39158

South Asian (SAS)

AF:

0.440

AC:

37120

AN:

84422

European-Finnish (FIN)

AF:

0.622

AC:

32702

AN:

52548

Middle Eastern (MID)

AF:

0.526

AC:

2967

AN:

5636

European-Non Finnish (NFE)

AF:

0.619

AC:

660838

AN:

1067298

Other (OTH)

AF:

0.570

AC:

33416

AN:

58600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

16168

32335

48503

64670

80838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.650

AC:

98764

AN:

151946

Hom.:

34288

Cov.:

AF XY:

0.641

AC XY:

47607

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.886

AC:

36712

AN:

41450

American (AMR)

AF:

0.499

AC:

7615

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

1791

AN:

3464

East Asian (EAS)

AF:

0.217

AC:

1123

AN:

5164

South Asian (SAS)

AF:

0.421

AC:

2029

AN:

4814

European-Finnish (FIN)

AF:

0.607

AC:

6396

AN:

10542

Middle Eastern (MID)

AF:

0.521

AC:

152

AN:

292

European-Non Finnish (NFE)

AF:

0.606

AC:

41192

AN:

67926

Other (OTH)

AF:

0.581

AC:

1226

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1541

3081

4622

6162

7703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.622

Hom.:

16449

Bravo

AF:

0.651

Asia WGS

AF:

0.331

AC:

1153

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.059

(source)

DANN

Benign

0.35

PhyloP100

-0.58

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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NM_001349206.2:c.1806+41G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over