rs13421506

Variant names:

• chr2-11724820-G-T
• rs13421506
• ENST00000396098.5:c.-72+178G>T

Variant summary

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

The ENST00000396098.5(LPIN1):​c.-72+178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,264 control chromosomes in the GnomAD database, including 660 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 0.083 (660 hom., cov: 32)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• 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, 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.138+11008G>T		intron_variant	Intron 2 of 21		NP_001248357.1
LPIN1	NM_001349207.2	c.82-40713G>T		intron_variant	Intron 1 of 20		NP_001336136.1
LPIN1	NM_001349208.2	c.138+11008G>T		intron_variant	Intron 2 of 20		NP_001336137.1
LPIN1	NM_001261427.3	c.-72+281G>T		intron_variant	Intron 1 of 20		NP_001248356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000396098.5	c.-72+178G>T		intron_variant	Intron 1 of 9	1		ENSP00000379405.1
LPIN1	ENST00000449576.6	c.138+11008G>T		intron_variant	Intron 2 of 21	2		ENSP00000397908.2
LPIN1	ENST00000396097.5	c.-72+281G>T		intron_variant	Intron 1 of 21	5		ENSP00000379404.2

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12581 AN: 152146 Hom.: 661 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0826 AC: 12582 AN: 152264 Hom.: 660 Cov.: 32 AF XY: 0.0811 AC XY: 6039 AN XY: 74448

African (AFR) AF: 0.149 AC: 6173 AN: 41520

American (AMR) AF: 0.0554 AC: 848 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3468

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5186

South Asian (SAS) AF: 0.0881 AC: 425 AN: 4822

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10620

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4249 AN: 68034

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0694 Hom.: 733

Bravo AF: 0.0851

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.47
PhyloP100		0.12
PromoterAI		0.025	Neutral
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: rs13421506; hg19: chr2-11864946;