rs3795974

chr2-11784824-T-C

Variant summary

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

The NM_001349206.2(LPIN1):c.1359-62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 1,517,020 control chromosomes in the GnomAD database, including 283,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31762 hom., cov: 34)
  • Exomes 𝑓: 0.60 (251726 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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 2-11784824-T-C is Benign according to our data. Variant chr2-11784824-T-C is described in ClinVar as [Benign]. Clinvar id is 683089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.1359-62T>C		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.1359-62T>C		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96784 AN: 152054 Hom.: 31729 Cov.: 34

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.601 AC: 820840 AN: 1364848 Hom.: 251726 Cov.: 22 AF XY: 0.596 AC XY: 408161 AN XY: 684492

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.536

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.622

Gnomad4 OTH exome AF: 0.585

GnomAD4 genome AF: 0.637 AC: 96875 AN: 152172 Hom.: 31762 Cov.: 34 AF XY: 0.631 AC XY: 46933 AN XY: 74388

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.599

Alfa AF: 0.606 Hom.: 47492

Bravo AF: 0.643

Asia WGS AF: 0.365 AC: 1273 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	-0.88
Cadd	Benign	1.8
Dann	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3795974; hg19: chr2-11924950; COSMIC: COSV56763184; COSMIC: COSV56763184;