rs7595221

Variant names:

• chr2-11756849-G-A
• rs7595221
• NM_001349206.2:c.-9-8684G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349206.2(LPIN1):​c.-9-8684G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,080 control chromosomes in the GnomAD database, including 27,897 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27897 hom., cov: 33)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.40
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.-9-8684G>A		intron_variant	Intron 1 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.-9-8684G>A		intron_variant	Intron 1 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89531 AN: 151962 Hom.: 27855 Cov.: 33

Gnomad AFR AF: 0.774

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.589 AC: 89627 AN: 152080 Hom.: 27897 Cov.: 33 AF XY: 0.580 AC XY: 43102 AN XY: 74312

African (AFR) AF: 0.775 AC: 32151 AN: 41486

American (AMR) AF: 0.473 AC: 7228 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1753 AN: 3470

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5174

South Asian (SAS) AF: 0.385 AC: 1855 AN: 4824

European-Finnish (FIN) AF: 0.536 AC: 5655 AN: 10544

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38144 AN: 67986

Other (OTH) AF: 0.544 AC: 1147 AN: 2108

Alfa AF: 0.559 Hom.: 40519

Bravo AF: 0.592

Asia WGS AF: 0.315 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0010
DANN	Benign	0.49
PhyloP100		-6.4
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: rs7595221; hg19: chr2-11896975;