rs201847019

Variant names:

• chr2-11782541-G-C
• rs201847019
• NM_001349206.2:c.1264+34G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-11782541-G-C
• chr2-11782541-G-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001349206.2(LPIN1):​c.1264+34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0420
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-11782541-G-C is Benign according to our data. Variant chr2-11782541-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 262581.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1264+34G>C		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.1411+34G>C		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.1354+34G>C		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.1264+34G>C		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.1156+34G>C		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000396098.5	TSL:1	c.1282+34G>C		intron	N/A	ENSP00000379405.1	Q14693-6

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152180 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000118 AC: 29 AN: 246246 AF XY: 0.000134

Gnomad AFR exome AF: 0.000131

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.000109

Gnomad OTH exome AF: 0.000665

GnomAD4 exome AF: 0.0000466 AC: 68 AN: 1460148 Hom.: 0 Cov.: 31 AF XY: 0.0000523 AC XY: 38 AN XY: 726340

African (AFR) AF: 0.0000598 AC: 2 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.000544 AC: 29 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4726

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111782

Other (OTH) AF: 0.000133 AC: 8 AN: 60248

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152298 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74460

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.40
DANN	Benign	0.69
PhyloP100		-0.042
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs201847019; hg19: chr2-11922667;