rs13421506

Positions:

• chr2-11724820-G-T

Variant summary

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

The ENST00000396098.5(LPIN1):​c.-72+178G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,264 control chromosomes in the GnomAD database, including 660 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 0.083 (660 hom., cov: 32)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001261427.3	c.-72+281G>T		intron_variant
LPIN1	NM_001261428.3	c.138+11008G>T		intron_variant
LPIN1	NM_001349207.2	c.82-40713G>T		intron_variant
LPIN1	NM_001349208.2	c.138+11008G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000396098.5	c.-72+178G>T		intron_variant		1
LPIN1	ENST00000396097.5	c.-72+281G>T		intron_variant		5
LPIN1	ENST00000425416.6	c.-72+281G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12581 AN: 152146 Hom.: 661 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0624

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0826 AC: 12582 AN: 152264 Hom.: 660 Cov.: 32 AF XY: 0.0811 AC XY: 6039 AN XY: 74448

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0554

Gnomad4 ASJ AF: 0.0741

Gnomad4 EAS AF: 0.0118

Gnomad4 SAS AF: 0.0881

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0625

Gnomad4 OTH AF: 0.0822

Alfa AF: 0.0675 Hom.: 557

Bravo AF: 0.0851

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13421506; hg19: chr2-11864946;