2-11713838-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001261428.3(LPIN1):c.138+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,434,026 control chromosomes in the GnomAD database, including 32,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (3223 hom., cov: 33)
  • Exomes 𝑓: 0.21 (29710 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.134

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-11713838-G-A is Benign according to our data. Variant chr2-11713838-G-A is described in ClinVar as [Benign]. Clinvar id is 683087.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001261428.3	c.138+26G>A		intron_variant
LPIN1	NM_001349207.2	c.81+36110G>A		intron_variant
LPIN1	NM_001349208.2	c.138+26G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000449576.6	c.138+26G>A		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27566 AN: 152078 Hom.: 3220 Cov.: 33

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.165

GnomAD3 exomes AF: 0.224 AC: 27625 AN: 123200 Hom.: 3422 AF XY: 0.226 AC XY: 15228 AN XY: 67296

Gnomad AFR exome AF: 0.0382

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.252

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.212 AC: 271860 AN: 1281830 Hom.: 29710 Cov.: 20 AF XY: 0.214 AC XY: 136510 AN XY: 636512

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.273

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.267

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.181 AC: 27565 AN: 152196 Hom.: 3223 Cov.: 33 AF XY: 0.185 AC XY: 13764 AN XY: 74396

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.162

Alfa AF: 0.244 Hom.: 6002

Bravo AF: 0.172

Asia WGS AF: 0.172 AC: 599 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myoglobinuria, acute recurrent, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.7
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4640359; hg19: chr2-11853964; COSMIC: COSV71938405;