chr2-11750302-C-G

Variant names:

• chr2-11750302-C-G
• rs10192566
• NM_001349206.2:c.-10+3631C>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.-10+3631C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,038 control chromosomes in the GnomAD database, including 22,971 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 0.53 (22971 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.-10+3631C>G		intron_variant	Intron 1 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.-10+3631C>G		intron_variant	Intron 1 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80895 AN: 151920 Hom.: 22936 Cov.: 32

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.533 AC: 80982 AN: 152038 Hom.: 22971 Cov.: 32 AF XY: 0.524 AC XY: 38959 AN XY: 74302

African (AFR) AF: 0.723 AC: 30000 AN: 41488

American (AMR) AF: 0.425 AC: 6505 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1531 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1084 AN: 5168

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4814

European-Finnish (FIN) AF: 0.469 AC: 4960 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33728 AN: 67926

Other (OTH) AF: 0.500 AC: 1055 AN: 2110

Alfa AF: 0.520 Hom.: 2793

Bravo AF: 0.535

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.60
PhyloP100		0.10
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: rs10192566; hg19: chr2-11890428;