rs11524

Variant names:

• chr2-11826191-T-C
• rs11524
• NM_001349206.2:c.*1400T>C

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.*1400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,530 control chromosomes in the GnomAD database, including 5,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (5212 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: LPIN1 NM_001349206.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.526
• Publications: 8 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=-0.84).
• BP6: Variant 2-11826191-T-C is Benign according to our data. Variant chr2-11826191-T-C is described in ClinVar as Benign. ClinVar VariationId is 330940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 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.*1400T>C		3_prime_UTR	Exon 21 of 21	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.*1400T>C		3_prime_UTR	Exon 22 of 22	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.*1400T>C		3_prime_UTR	Exon 21 of 21	NP_001336136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000674199.1	MANE Select	c.*1400T>C		3_prime_UTR	Exon 21 of 21	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.*1400T>C		3_prime_UTR	Exon 20 of 20	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.3666T>C		non_coding_transcript_exon	Exon 16 of 16

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31887 AN: 151982 Hom.: 5174 Cov.: 32

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.0419 AC: 18 AN: 430 Hom.: 0 Cov.: 0 AF XY: 0.0349 AC XY: 9 AN XY: 258

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: 0.0425 AC: 18 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

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

GnomAD4 genome AF: 0.210 AC: 31971 AN: 152100 Hom.: 5212 Cov.: 32 AF XY: 0.207 AC XY: 15392 AN XY: 74372

African (AFR) AF: 0.446 AC: 18467 AN: 41420

American (AMR) AF: 0.173 AC: 2649 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3468

East Asian (EAS) AF: 0.167 AC: 864 AN: 5186

South Asian (SAS) AF: 0.0939 AC: 453 AN: 4824

European-Finnish (FIN) AF: 0.0571 AC: 605 AN: 10602

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7657 AN: 68006

Other (OTH) AF: 0.184 AC: 388 AN: 2108

Alfa AF: 0.137 Hom.: 1010

Bravo AF: 0.233

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

ClinVar submissions

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	-0.84
CADD	Benign	0.29
DANN	Benign	0.50
PhyloP100		-0.53
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: rs11524; hg19: chr2-11966317; COSMIC: COSV56764839; COSMIC: COSV56764839;