2-11713837-C-T

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.138+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,458,688 control chromosomes in the GnomAD database, including 7,393 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.074 (561 hom., cov: 33)
  • Exomes 𝑓: 0.096 (6832 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.826

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=-0.88).
• BP6: Variant 2-11713837-C-T is Benign according to our data. Variant chr2-11713837-C-T is described in ClinVar as [Benign]. Clinvar id is 1270822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001261428.3	c.138+25C>T		intron_variant
LPIN1	NM_001349207.2	c.81+36109C>T		intron_variant
LPIN1	NM_001349208.2	c.138+25C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000449576.6	c.138+25C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0742 AC: 11281 AN: 152098 Hom.: 564 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0949

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0856

GnomAD3 exomes AF: 0.0723 AC: 8865 AN: 122548 Hom.: 408 AF XY: 0.0723 AC XY: 4837 AN XY: 66888

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.000196

Gnomad SAS exome AF: 0.0374

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0880

GnomAD4 exome AF: 0.0963 AC: 125755 AN: 1306472 Hom.: 6832 Cov.: 21 AF XY: 0.0954 AC XY: 61762 AN XY: 647680

Gnomad4 AFR exome AF: 0.0146

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.000169

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.0982

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0882

GnomAD4 genome AF: 0.0741 AC: 11272 AN: 152216 Hom.: 561 Cov.: 33 AF XY: 0.0731 AC XY: 5438 AN XY: 74410

Gnomad4 AFR AF: 0.0193

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0949

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.105 Hom.: 250

Bravo AF: 0.0697

Asia WGS AF: 0.0150 AC: 53 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

Jul 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62113260; hg19: chr2-11853963;