2-11713596-T-C

Variant names:

• chr2-11713596-T-C
• rs73181378
• NM_001261428.3:c.82-160T>C

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.82-160T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0585 in 152,224 control chromosomes in the GnomAD database, including 614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.058 (614 hom., cov: 33)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.252

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=-0.94).
• BP6: Variant 2-11713596-T-C is Benign according to our data. Variant chr2-11713596-T-C is described in ClinVar as [Benign]. Clinvar id is 670680.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.82-160T>C		intron_variant	Intron 1 of 21		NP_001248357.1
LPIN1	NM_001349207.2	c.81+35868T>C		intron_variant	Intron 1 of 20		NP_001336136.1
LPIN1	NM_001349208.2	c.82-160T>C		intron_variant	Intron 1 of 20		NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.82-160T>C		intron_variant	Intron 1 of 21	2		ENSP00000397908.2

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8884 AN: 152106 Hom.: 612 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0638

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0487

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

GnomAD4 genome AF: 0.0585 AC: 8898 AN: 152224 Hom.: 614 Cov.: 33 AF XY: 0.0568 AC XY: 4228 AN XY: 74416

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.0334

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0383 Hom.: 40

Bravo AF: 0.0660

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.94
CADD	Benign	4.4
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73181378; hg19: chr2-11853722;