rs10209969

Variant names:

• chr2-11765750-C-T
• rs10209969
• NM_001349206.2:c.192+17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001349206.2(LPIN1):​c.192+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,602,574 control chromosomes in the GnomAD database, including 86,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6129 hom., cov: 32)
  • Exomes 𝑓: 0.33 (80663 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.03
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-11765750-C-T is Benign according to our data. Variant chr2-11765750-C-T is described in ClinVar as Benign. ClinVar VariationId is 96495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.339 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.192+17C>T		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.339+17C>T		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.282+17C>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.192+17C>T		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.192+17C>T		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000396098.5	TSL:1	c.210+17C>T		intron	N/A	ENSP00000379405.1	Q14693-6

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39988 AN: 151890 Hom.: 6131 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.272

GnomAD2 exomes AF: 0.295 AC: 72810 AN: 246696 AF XY: 0.302

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.295

Gnomad EAS exome AF: 0.202

Gnomad FIN exome AF: 0.360

Gnomad NFE exome AF: 0.347

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.330 AC: 478202 AN: 1450564 Hom.: 80663 Cov.: 32 AF XY: 0.329 AC XY: 236794 AN XY: 720010

African (AFR) AF: 0.101 AC: 3365 AN: 33324

American (AMR) AF: 0.241 AC: 10695 AN: 44294

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 7510 AN: 25730

East Asian (EAS) AF: 0.228 AC: 8977 AN: 39452

South Asian (SAS) AF: 0.283 AC: 24202 AN: 85554

European-Finnish (FIN) AF: 0.369 AC: 19632 AN: 53220

Middle Eastern (MID) AF: 0.391 AC: 2215 AN: 5662

European-Non Finnish (NFE) AF: 0.347 AC: 382938 AN: 1103514

Other (OTH) AF: 0.312 AC: 18668 AN: 59814

GnomAD4 genome AF: 0.263 AC: 39981 AN: 152010 Hom.: 6129 Cov.: 32 AF XY: 0.263 AC XY: 19543 AN XY: 74292

African (AFR) AF: 0.107 AC: 4453 AN: 41502

American (AMR) AF: 0.280 AC: 4280 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3466

East Asian (EAS) AF: 0.211 AC: 1085 AN: 5140

South Asian (SAS) AF: 0.267 AC: 1283 AN: 4804

European-Finnish (FIN) AF: 0.353 AC: 3724 AN: 10550

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23267 AN: 67952

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.306 Hom.: 2418

Bravo AF: 0.247

Asia WGS AF: 0.192 AC: 667 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Myoglobinuria, acute recurrent, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.62
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10209969; hg19: chr2-11905876; COSMIC: COSV56770465; COSMIC: COSV56770465;