rs893345

Variant names:

• chr2-11744990-G-A
• rs893345
• ENST00000396098.5:c.9+3562G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-11744990-G-A
• chr2-11744990-G-T

Variant summary

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

The NM_001261428.3(LPIN1):​c.139-20543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,156 control chromosomes in the GnomAD database, including 11,801 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 0.37 (11801 hom., cov: 33)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 2 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

LOC124907735 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261428.3. 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_001261428.3		c.139-20543G>A		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.82-20543G>A		intron	N/A	NP_001336136.1
	LPIN1	NM_001349208.2		c.139-20543G>A		intron	N/A	NP_001336137.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000396098.5	TSL:1	c.9+3562G>A		intron	N/A	ENSP00000379405.1	Q14693-6
	LPIN1	ENST00000449576.6	TSL:2	c.139-20543G>A		intron	N/A	ENSP00000397908.2	Q14693-7
	LPIN1	ENST00000396097.5	TSL:5	c.9+3562G>A		intron	N/A	ENSP00000379404.2	Q14693-5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56680 AN: 152036 Hom.: 11802 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.373 AC: 56695 AN: 152156 Hom.: 11801 Cov.: 33 AF XY: 0.369 AC XY: 27427 AN XY: 74376

African (AFR) AF: 0.203 AC: 8413 AN: 41514

American (AMR) AF: 0.383 AC: 5855 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1470 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1195 AN: 5176

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4820

European-Finnish (FIN) AF: 0.405 AC: 4283 AN: 10584

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32622 AN: 67982

Other (OTH) AF: 0.402 AC: 848 AN: 2110

Alfa AF: 0.393 Hom.: 4651

Bravo AF: 0.361

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.77
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs893345; hg19: chr2-11885116;