rs17603420

Variant names:

• chr2-11789614-G-A
• rs17603420
• NM_001349206.2:c.1713+1158G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349206.2(LPIN1):​c.1713+1158G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,104 control chromosomes in the GnomAD database, including 21,930 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (21930 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 3 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: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349206.2. 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_001349206.2	MANE Select	c.1713+1158G>A		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.1860+1158G>A		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1803+1158G>A		intron	N/A	NP_001336136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000674199.1	MANE Select	c.1713+1158G>A		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1605+1158G>A		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1198+1158G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77945 AN: 151986 Hom.: 21891 Cov.: 33

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.513 AC: 78034 AN: 152104 Hom.: 21930 Cov.: 33 AF XY: 0.507 AC XY: 37711 AN XY: 74358

African (AFR) AF: 0.750 AC: 31122 AN: 41516

American (AMR) AF: 0.389 AC: 5936 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1296 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1110 AN: 5176

South Asian (SAS) AF: 0.347 AC: 1669 AN: 4814

European-Finnish (FIN) AF: 0.505 AC: 5344 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30118 AN: 67964

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.479 Hom.: 30772

Bravo AF: 0.514

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.032
DANN	Benign	0.40
PhyloP100		-0.88
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17603420; hg19: chr2-11929740;