NM_001349206.2:c.1886+3405G>A

Variant names:

• chr2-11798892-G-A
• rs17603755
• NM_001349206.2:c.1886+3405G>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.1886+3405G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,150 control chromosomes in the GnomAD database, including 1,006 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 0.11 (1006 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• 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: 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 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.1886+3405G>A		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.2033+3405G>A		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1976+3405G>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.1886+3405G>A		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1778+3405G>A		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1371+3405G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16779 AN: 152034 Hom.: 1007 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.110 AC: 16776 AN: 152150 Hom.: 1006 Cov.: 32 AF XY: 0.109 AC XY: 8073 AN XY: 74382

African (AFR) AF: 0.0546 AC: 2266 AN: 41494

American (AMR) AF: 0.110 AC: 1687 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.0869 AC: 450 AN: 5180

South Asian (SAS) AF: 0.0794 AC: 383 AN: 4826

European-Finnish (FIN) AF: 0.154 AC: 1627 AN: 10574

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9512 AN: 68000

Other (OTH) AF: 0.130 AC: 274 AN: 2108

Alfa AF: 0.117 Hom.: 412

Bravo AF: 0.105

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.4
DANN	Benign	0.96
PhyloP100		-0.18
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: rs17603755; hg19: chr2-11939018;