rs6744682

Positions:

• chr2-11789202-A-T

Variant summary

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

The NM_001349206.2(LPIN1):​c.1713+746A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,186 control chromosomes in the GnomAD database, including 17,819 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 0.43 (17819 hom., cov: 34)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.1713+746A>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.1713+746A>T		intron_variant			NM_001349206.2	ENSP00000501331	P4

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64741 AN: 152068 Hom.: 17767 Cov.: 34

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0660

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.426 AC: 64852 AN: 152186 Hom.: 17819 Cov.: 34 AF XY: 0.420 AC XY: 31260 AN XY: 74402

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0661

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.341

Alfa AF: 0.379 Hom.: 1696

Bravo AF: 0.436

Asia WGS AF: 0.188 AC: 654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.12
DANN	Benign	0.63

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: rs6744682; hg19: chr2-11929328;