2-11798820-G-A

Variant names:

• chr2-11798820-G-A
• rs2577262
• NM_001349206.2:c.1886+3333G>A

Variant summary

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

The NM_001349206.2(LPIN1):​c.1886+3333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,174 control chromosomes in the GnomAD database, including 14,889 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 0.40 (14889 hom., cov: 31)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 9 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• 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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	NM_001349206.2	MANE Select	c.1886+3333G>A		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.2033+3333G>A		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1976+3333G>A		intron	N/A	NP_001336136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000674199.1	MANE Select	c.1886+3333G>A		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1778+3333G>A		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1371+3333G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60562 AN: 151082 Hom.: 14850 Cov.: 31

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.401 AC: 60656 AN: 151174 Hom.: 14889 Cov.: 31 AF XY: 0.397 AC XY: 29295 AN XY: 73766

African (AFR) AF: 0.698 AC: 28833 AN: 41330

American (AMR) AF: 0.279 AC: 4236 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.0652 AC: 336 AN: 5152

South Asian (SAS) AF: 0.262 AC: 1253 AN: 4774

European-Finnish (FIN) AF: 0.361 AC: 3674 AN: 10168

Middle Eastern (MID) AF: 0.183 AC: 52 AN: 284

European-Non Finnish (NFE) AF: 0.302 AC: 20485 AN: 67830

Other (OTH) AF: 0.322 AC: 674 AN: 2090

Alfa AF: 0.368 Hom.: 3623

Bravo AF: 0.406

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.15
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: rs2577262; hg19: chr2-11938946;