rs11890442

Positions:

• chr2-11770877-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349206.2(LPIN1):​c.289-495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,020 control chromosomes in the GnomAD database, including 10,458 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 0.31 (10458 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.289-495C>T		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.289-495C>T		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47547 AN: 151902 Hom.: 10419 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.00463

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.313 AC: 47644 AN: 152020 Hom.: 10458 Cov.: 32 AF XY: 0.305 AC XY: 22664 AN XY: 74320

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.00483

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.265

Alfa AF: 0.278 Hom.: 1003

Bravo AF: 0.330

Asia WGS AF: 0.123 AC: 428 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	1.8
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs11890442; hg19: chr2-11911003;