chr2-11713596-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• myoglobinuria, acute recurrent, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Laboratory for Molecular Medicine, PanelApp Australia
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261428.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	NM_001261428.3		c.82-160T>C		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.81+35868T>C		intron	N/A	NP_001336136.1
	LPIN1	NM_001349208.2		c.82-160T>C		intron	N/A	NP_001336137.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000449576.6	TSL:2	c.82-160T>C		intron	N/A	ENSP00000397908.2	Q14693-7
	LPIN1	ENST00000852426.1		c.-66-160T>C		intron	N/A	ENSP00000522485.1
	LPIN1	ENST00000961822.1		c.-66-160T>C		intron	N/A	ENSP00000631881.1

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

African (AFR) AF: 0.165 AC: 6857 AN: 41502

American (AMR) AF: 0.0303 AC: 463 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.0632 AC: 327 AN: 5178

South Asian (SAS) AF: 0.0334 AC: 161 AN: 4818

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 846 AN: 68022

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0383 Hom.: 40

Bravo AF: 0.0660

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs73181378; hg19: chr2-11853722;