2-11713886-G-A

Position:

• chr2-11713886-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+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,095,936 control chromosomes in the GnomAD database, including 11,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1990 hom., cov: 33)
  • Exomes 𝑓: 0.13 (9196 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71

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=-0.96).
• BP6: Variant 2-11713886-G-A is Benign according to our data. Variant chr2-11713886-G-A is described in ClinVar as [Benign]. Clinvar id is 670695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.138+74G>A		intron_variant			NP_001248357.1
LPIN1	NM_001349207.2	c.81+36158G>A		intron_variant			NP_001336136.1
LPIN1	NM_001349208.2	c.138+74G>A		intron_variant			NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.138+74G>A		intron_variant		2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23396 AN: 152104 Hom.: 1987 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0855

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.134 AC: 126154 AN: 943714 Hom.: 9196 AF XY: 0.131 AC XY: 62837 AN XY: 479840

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.0763

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.154 AC: 23424 AN: 152222 Hom.: 1990 Cov.: 33 AF XY: 0.154 AC XY: 11439 AN XY: 74424

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.0862

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.155

Alfa AF: 0.134 Hom.: 2889

Bravo AF: 0.159

Asia WGS AF: 0.183 AC: 638 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10182021; hg19: chr2-11854012; COSMIC: COSV71938406;