rs1050800

Variant names:

• chr2-11825688-C-T
• rs1050800
• ENST00000404113.6:n.3163C>T

Variant summary

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

The ENST00000404113.6(LPIN1):​n.3163C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,518 control chromosomes in the GnomAD database, including 1,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1403 hom., cov: 32)
  • Exomes 𝑓: 0.19 (9 hom.)
• Consequence: LPIN1 ENST00000404113.6 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83
• Publications: 15 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• 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=-0.55).
• BP6: Variant 2-11825688-C-T is Benign according to our data. Variant chr2-11825688-C-T is described in ClinVar as Benign. ClinVar VariationId is 330932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404113.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	NM_001349206.2	MANE Select	c.*897C>T		3_prime_UTR	Exon 21 of 21	NP_001336135.1
	LPIN1	NR_146080.2		n.3771C>T		non_coding_transcript_exon	Exon 20 of 20
	LPIN1	NM_001261428.3		c.*897C>T		3_prime_UTR	Exon 22 of 22	NP_001248357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000404113.6	TSL:1	n.3163C>T		non_coding_transcript_exon	Exon 16 of 16
	LPIN1	ENST00000674199.1	MANE Select	c.*897C>T		3_prime_UTR	Exon 21 of 21	ENSP00000501331.1
	LPIN1	ENST00000256720.6	TSL:1	c.*897C>T		3_prime_UTR	Exon 20 of 20	ENSP00000256720.2

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18639 AN: 152028 Hom.: 1405 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.188 AC: 70 AN: 372 Hom.: 9 Cov.: 0 AF XY: 0.192 AC XY: 43 AN XY: 224

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.190 AC: 70 AN: 368

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.122 AC: 18632 AN: 152146 Hom.: 1403 Cov.: 32 AF XY: 0.122 AC XY: 9083 AN XY: 74384

African (AFR) AF: 0.0377 AC: 1563 AN: 41512

American (AMR) AF: 0.141 AC: 2154 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1137 AN: 5170

South Asian (SAS) AF: 0.111 AC: 536 AN: 4816

European-Finnish (FIN) AF: 0.162 AC: 1710 AN: 10570

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10728 AN: 68000

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.137 Hom.: 3045

Bravo AF: 0.118

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.1
DANN	Benign	0.79
PhyloP100		1.8
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: rs1050800; hg19: chr2-11965814;