2-11794630-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001349206.2(LPIN1):c.1807-778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 138,614 control chromosomes in the GnomAD database, including 33 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 0.013 (33 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170

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=-0.93).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.013 (1807/138614) while in subpopulation SAS AF= 0.0473 (211/4460). AF 95% confidence interval is 0.0421. There are 33 homozygotes in gnomad4. There are 883 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.1807-778C>T		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.1807-778C>T		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1807 AN: 138494 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00286

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.00213

Gnomad MID AF: 0.0458

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0188

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

GnomAD4 genome AF: 0.0130 AC: 1807 AN: 138614 Hom.: 33 Cov.: 33 AF XY: 0.0131 AC XY: 883 AN XY: 67568

Gnomad4 AFR AF: 0.00285

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.0312

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.00213

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0186

Alfa AF: 0.00517 Hom.: 2

Bravo AF: 0.0115

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.7
Dann	Benign	0.82

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: rs6729430; hg19: chr2-11934756;