rs16857866

Variant names:

• chr2-11770592-C-T
• rs16857866
• NM_001349206.2:c.289-780C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349206.2(LPIN1):​c.289-780C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,164 control chromosomes in the GnomAD database, including 4,905 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 0.15 (4905 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	NM_001349206.2	MANE Select	c.289-780C>T		intron	N/A	NP_001336135.1
	LPIN1	NM_001261428.3		c.436-780C>T		intron	N/A	NP_001248357.1
	LPIN1	NM_001349207.2		c.379-780C>T		intron	N/A	NP_001336136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000674199.1	MANE Select	c.289-780C>T		intron	N/A	ENSP00000501331.1
	LPIN1	ENST00000256720.6	TSL:1	c.289-780C>T		intron	N/A	ENSP00000256720.2
	LPIN1	ENST00000396098.5	TSL:1	c.307-780C>T		intron	N/A	ENSP00000379405.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22621 AN: 152046 Hom.: 4880 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.149 AC: 22698 AN: 152164 Hom.: 4905 Cov.: 33 AF XY: 0.144 AC XY: 10735 AN XY: 74416

African (AFR) AF: 0.481 AC: 19907 AN: 41424

American (AMR) AF: 0.0685 AC: 1047 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00923 AC: 32 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5194

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4826

European-Finnish (FIN) AF: 0.0122 AC: 130 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1211 AN: 68020

Other (OTH) AF: 0.106 AC: 224 AN: 2112

Alfa AF: 0.0844 Hom.: 1010

Bravo AF: 0.171

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.81
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16857866; hg19: chr2-11910718;