rs893346

Variant names:

• chr2-11742635-A-G
• rs893346
• ENST00000396098.5:c.9+1207A>G

Variant summary

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

The ENST00000396098.5(LPIN1):​c.9+1207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,130 control chromosomes in the GnomAD database, including 7,714 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 0.22 (7714 hom., cov: 33)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 10 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

ENSG00000230790 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.139-22898A>G		intron_variant	Intron 2 of 21		NP_001248357.1
LPIN1	NM_001349207.2	c.82-22898A>G		intron_variant	Intron 1 of 20		NP_001336136.1
LPIN1	NM_001349208.2	c.139-22898A>G		intron_variant	Intron 2 of 20		NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000396098.5	c.9+1207A>G		intron_variant	Intron 2 of 9	1		ENSP00000379405.1
LPIN1	ENST00000449576.6	c.139-22898A>G		intron_variant	Intron 2 of 21	2		ENSP00000397908.2
LPIN1	ENST00000396097.5	c.9+1207A>G		intron_variant	Intron 2 of 21	5		ENSP00000379404.2

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32869 AN: 152012 Hom.: 7695 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.217 AC: 32946 AN: 152130 Hom.: 7714 Cov.: 33 AF XY: 0.211 AC XY: 15691 AN XY: 74380

African (AFR) AF: 0.591 AC: 24503 AN: 41472

American (AMR) AF: 0.0983 AC: 1503 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5180

South Asian (SAS) AF: 0.0580 AC: 280 AN: 4828

European-Finnish (FIN) AF: 0.106 AC: 1119 AN: 10600

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0710 AC: 4829 AN: 67972

Other (OTH) AF: 0.154 AC: 325 AN: 2114

Alfa AF: 0.129 Hom.: 5900

Bravo AF: 0.235

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.34
PhyloP100		-1.1
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: rs893346; hg19: chr2-11882761;