rs1050800

Positions:

• chr2-11825688-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349206.2(LPIN1):​c.*897C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,518 control chromosomes in the GnomAD database, including 1,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1403 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9 hom.)
• Consequence: LPIN1 NM_001349206.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83

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]

LPIN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-11825688-C-T is Benign according to our data. Variant chr2-11825688-C-T is described in ClinVar as [Benign]. Clinvar id is 330932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.*897C>T		3_prime_UTR_variant	21/21	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.*897C>T		3_prime_UTR_variant	21/21		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18639 AN: 152028 Hom.: 1405 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.188 AC: 70 AN: 372 Hom.: 9 Cov.: 0 AF XY: 0.192 AC XY: 43 AN XY: 224

Gnomad4 FIN exome AF: 0.190

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.122 AC: 18632 AN: 152146 Hom.: 1403 Cov.: 32 AF XY: 0.122 AC XY: 9083 AN XY: 74384

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0968

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.116

Alfa AF: 0.149 Hom.: 2344

Bravo AF: 0.118

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myoglobinuria, acute recurrent, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

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	-0.55
CADD	Benign	8.1
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1050800; hg19: chr2-11965814;