rs16857866

Positions:

• chr2-11770592-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.289-780C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,164 control chromosomes in the GnomAD database, including 4,905 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 0.15 (4905 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.289-780C>T		intron_variant		ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.289-780C>T		intron_variant			NM_001349206.2	ENSP00000501331	P4

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22621 AN: 152046 Hom.: 4880 Cov.: 33

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0122

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.149 AC: 22698 AN: 152164 Hom.: 4905 Cov.: 33 AF XY: 0.144 AC XY: 10735 AN XY: 74416

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.0685

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0122

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0778 Hom.: 818

Bravo AF: 0.171

Asia WGS AF: 0.0640 AC: 222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.81

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: rs16857866; hg19: chr2-11910718;