2-11800661-T-G

Variant names:

• chr2-11800661-T-G
• rs2577261
• NM_001349206.2:c.1887-2246T>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.1887-2246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,234 control chromosomes in the GnomAD database, including 64,206 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 0.92 (64206 hom., cov: 31)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.1887-2246T>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.1887-2246T>G		intron_variant	Intron 14 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139650 AN: 152116 Hom.: 64156 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.918 AC: 139760 AN: 152234 Hom.: 64206 Cov.: 31 AF XY: 0.916 AC XY: 68199 AN XY: 74416

African (AFR) AF: 0.927 AC: 38498 AN: 41532

American (AMR) AF: 0.942 AC: 14405 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3302 AN: 3468

East Asian (EAS) AF: 0.944 AC: 4886 AN: 5174

South Asian (SAS) AF: 0.961 AC: 4636 AN: 4824

European-Finnish (FIN) AF: 0.860 AC: 9114 AN: 10592

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61801 AN: 68028

Other (OTH) AF: 0.931 AC: 1966 AN: 2112

Alfa AF: 0.917 Hom.: 32242

Bravo AF: 0.924

Asia WGS AF: 0.940 AC: 3269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.75
PhyloP100		-0.39
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: rs2577261; hg19: chr2-11940787;