chr2-11793260-A-G

Variant names:

• chr2-11793260-A-G
• rs10520097
• NM_001349206.2:c.1806+1254A>G

Variant summary

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

The NM_001349206.2(LPIN1):​c.1806+1254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,148 control chromosomes in the GnomAD database, including 1,161 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 0.12 (1161 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 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.1806+1254A>G		intron	N/A	NP_001336135.1
	LPIN1	NM_001261428.3		c.1953+1254A>G		intron	N/A	NP_001248357.1
	LPIN1	NM_001349207.2		c.1896+1254A>G		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.1806+1254A>G		intron	N/A	ENSP00000501331.1
	LPIN1	ENST00000256720.6	TSL:1	c.1698+1254A>G		intron	N/A	ENSP00000256720.2
	LPIN1	ENST00000404113.6	TSL:1	n.1291+1254A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18576 AN: 152028 Hom.: 1161 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.122 AC: 18581 AN: 152148 Hom.: 1161 Cov.: 32 AF XY: 0.121 AC XY: 8991 AN XY: 74372

African (AFR) AF: 0.0863 AC: 3581 AN: 41504

American (AMR) AF: 0.115 AC: 1753 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3472

East Asian (EAS) AF: 0.148 AC: 768 AN: 5172

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1623 AN: 10580

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9565 AN: 67984

Other (OTH) AF: 0.134 AC: 283 AN: 2114

Alfa AF: 0.134 Hom.: 1132

Bravo AF: 0.118

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0060
DANN	Benign	0.31
PhyloP100		-2.7
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: rs10520097; hg19: chr2-11933386;