chr2-11713629-G-A

Position:

• chr2-11713629-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001261428.3(LPIN1):​c.82-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 592,308 control chromosomes in the GnomAD database, including 5,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1715 hom., cov: 33)
  • Exomes 𝑓: 0.12 (3712 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 2-11713629-G-A is Benign according to our data. Variant chr2-11713629-G-A is described in ClinVar as [Benign]. Clinvar id is 670679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.82-127G>A		intron_variant			NP_001248357.1
LPIN1	NM_001349207.2	c.81+35901G>A		intron_variant			NP_001336136.1
LPIN1	NM_001349208.2	c.82-127G>A		intron_variant			NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.82-127G>A		intron_variant		2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21172 AN: 151860 Hom.: 1715 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.120 AC: 52835 AN: 440330 Hom.: 3712 AF XY: 0.116 AC XY: 26983 AN XY: 232328

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.0989

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.0591

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.139 AC: 21190 AN: 151978 Hom.: 1715 Cov.: 33 AF XY: 0.139 AC XY: 10331 AN XY: 74258

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0993

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.140

Alfa AF: 0.128 Hom.: 187

Bravo AF: 0.144

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-1.0
CADD	Benign	0.27
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10179409; hg19: chr2-11853755;