2-11794630-C-T

Variant names:

• chr2-11794630-C-T
• rs6729430
• NM_001349206.2:c.1807-778C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001349206.2(LPIN1):​c.1807-778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 138,614 control chromosomes in the GnomAD database, including 33 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 0.013 (33 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• 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=-0.93).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.013 (1807/138614) while in subpopulation SAS AF = 0.0473 (211/4460). AF 95% confidence interval is 0.0421. There are 33 homozygotes in GnomAd4. There are 883 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR,AD gene

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.1807-778C>T		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.1954-778C>T		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1897-778C>T		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.1807-778C>T		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1699-778C>T		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1292-778C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1807 AN: 138494 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.00286

Gnomad AMI AF: 0.0683

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0312

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0473

Gnomad FIN AF: 0.00213

Gnomad MID AF: 0.0458

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0188

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

GnomAD4 genome AF: 0.0130 AC: 1807 AN: 138614 Hom.: 33 Cov.: 33 AF XY: 0.0131 AC XY: 883 AN XY: 67568

African (AFR) AF: 0.00285 AC: 102 AN: 35826

American (AMR) AF: 0.0143 AC: 206 AN: 14386

Ashkenazi Jewish (ASJ) AF: 0.0312 AC: 104 AN: 3332

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5140

South Asian (SAS) AF: 0.0473 AC: 211 AN: 4460

European-Finnish (FIN) AF: 0.00213 AC: 20 AN: 9374

Middle Eastern (MID) AF: 0.0458 AC: 13 AN: 284

European-Non Finnish (NFE) AF: 0.0167 AC: 1051 AN: 62986

Other (OTH) AF: 0.0186 AC: 37 AN: 1992

Alfa AF: 0.0127 Hom.: 21

Bravo AF: 0.0115

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.82
PhyloP100		-0.017
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6729430;

hg19: chr2-11934756;