chr2-11713457-G-T

Variant names:

• chr2-11713457-G-T
• rs13398067
• NM_001261428.3:c.82-299G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001261428.3(LPIN1):​c.82-299G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,172 control chromosomes in the GnomAD database, including 1,989 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1989 hom., cov: 33)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00200
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Laboratory for Molecular Medicine, PanelApp Australia
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-11713457-G-T is Benign according to our data. Variant chr2-11713457-G-T is described in ClinVar as Benign. ClinVar VariationId is 1247440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001261428.3. 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_001261428.3		c.82-299G>T		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.81+35729G>T		intron	N/A	NP_001336136.1
	LPIN1	NM_001349208.2		c.82-299G>T		intron	N/A	NP_001336137.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000449576.6	TSL:2	c.82-299G>T		intron	N/A	ENSP00000397908.2	Q14693-7
	LPIN1	ENST00000852426.1		c.-66-299G>T		intron	N/A	ENSP00000522485.1
	LPIN1	ENST00000961822.1		c.-66-299G>T		intron	N/A	ENSP00000631881.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23318 AN: 152054 Hom.: 1985 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.153 AC: 23347 AN: 152172 Hom.: 1989 Cov.: 33 AF XY: 0.153 AC XY: 11414 AN XY: 74406

African (AFR) AF: 0.204 AC: 8457 AN: 41502

American (AMR) AF: 0.137 AC: 2096 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.299 AC: 1546 AN: 5174

South Asian (SAS) AF: 0.0856 AC: 413 AN: 4826

European-Finnish (FIN) AF: 0.111 AC: 1172 AN: 10588

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8692 AN: 68008

Other (OTH) AF: 0.156 AC: 331 AN: 2116

Alfa AF: 0.142 Hom.: 218

Bravo AF: 0.158

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13398067; hg19: chr2-11853583;