rs11693809

chr2-11750012-T-Cchr2-11750012-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.-10+3341T>C		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.-10+3341T>C		intron_variant			NM_001349206.2	P4

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

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.611

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.3
Dann	Benign	0.58

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: rs11693809; hg19: chr2-11890138;