rs2577264

Variant names:

• chr2-11796672-A-G
• rs2577264
• NM_001349206.2:c.1886+1185A>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.1886+1185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,978 control chromosomes in the GnomAD database, including 34,299 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 0.65 (34299 hom., cov: 31)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 20 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.1886+1185A>G		intron_variant	Intron 14 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.1886+1185A>G		intron_variant	Intron 14 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98456 AN: 151860 Hom.: 34246 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.607

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.648 AC: 98556 AN: 151978 Hom.: 34299 Cov.: 31 AF XY: 0.639 AC XY: 47446 AN XY: 74258

African (AFR) AF: 0.886 AC: 36737 AN: 41478

American (AMR) AF: 0.499 AC: 7622 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1772 AN: 3468

East Asian (EAS) AF: 0.157 AC: 812 AN: 5162

South Asian (SAS) AF: 0.421 AC: 2026 AN: 4814

European-Finnish (FIN) AF: 0.608 AC: 6400 AN: 10524

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.607 AC: 41273 AN: 67946

Other (OTH) AF: 0.585 AC: 1234 AN: 2108

Alfa AF: 0.604 Hom.: 48120

Bravo AF: 0.648

Asia WGS AF: 0.316 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.6
DANN	Benign	0.43
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs2577264; hg19: chr2-11936798; COSMIC: COSV56765166; COSMIC: COSV56765166;