rs11693809

Variant names:

• chr2-11750012-T-C
• rs11693809
• NM_001349206.2:c.-10+3341T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-11750012-T-C
• chr2-11750012-T-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+3341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,128 control chromosomes in the GnomAD database, including 35,412 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 0.66 (35412 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 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.-10+3341T>C		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.139-15521T>C		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.82-15521T>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.-10+3341T>C		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.-10+3341T>C		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000396098.5	TSL:1	c.9+8584T>C		intron	N/A	ENSP00000379405.1	Q14693-6

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100466 AN: 152010 Hom.: 35363 Cov.: 33

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.661 AC: 100571 AN: 152128 Hom.: 35412 Cov.: 33 AF XY: 0.650 AC XY: 48345 AN XY: 74368

African (AFR) AF: 0.883 AC: 36692 AN: 41538

American (AMR) AF: 0.517 AC: 7900 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1796 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1103 AN: 5180

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4822

European-Finnish (FIN) AF: 0.613 AC: 6482 AN: 10578

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42726 AN: 67940

Other (OTH) AF: 0.611 AC: 1292 AN: 2114

Alfa AF: 0.562 Hom.: 1830

Bravo AF: 0.662

Asia WGS AF: 0.325 AC: 1133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		-2.1
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: rs11693809; hg19: chr2-11890138;