2-11797032-G-C

Variant names:

• chr2-11797032-G-C
• rs6708316
• NM_001349206.2:c.1886+1545G>C

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+1545G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,058 control chromosomes in the GnomAD database, including 12,219 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 0.38 (12219 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 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+1545G>C		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.2033+1545G>C		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1976+1545G>C		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+1545G>C		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1778+1545G>C		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1371+1545G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57156 AN: 151940 Hom.: 12191 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.0657

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.376 AC: 57240 AN: 152058 Hom.: 12219 Cov.: 32 AF XY: 0.374 AC XY: 27791 AN XY: 74312

African (AFR) AF: 0.578 AC: 23961 AN: 41464

American (AMR) AF: 0.282 AC: 4306 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 857 AN: 3470

East Asian (EAS) AF: 0.0659 AC: 341 AN: 5176

South Asian (SAS) AF: 0.271 AC: 1308 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3842 AN: 10542

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21573 AN: 67984

Other (OTH) AF: 0.309 AC: 653 AN: 2110

Alfa AF: 0.191 Hom.: 381

Bravo AF: 0.378

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.43
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: rs6708316; hg19: chr2-11937158;