chr2-11800661-T-G

Variant names:

• chr2-11800661-T-G
• rs2577261
• NM_001349206.2:c.1887-2246T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349206.2(LPIN1):​c.1887-2246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,234 control chromosomes in the GnomAD database, including 64,206 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 0.92 (64206 hom., cov: 31)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.1887-2246T>G		intron_variant	Intron 14 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.1887-2246T>G		intron_variant	Intron 14 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139650 AN: 152116 Hom.: 64156 Cov.: 31

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.918 AC: 139760 AN: 152234 Hom.: 64206 Cov.: 31 AF XY: 0.916 AC XY: 68199 AN XY: 74416

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.961

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.931

Alfa AF: 0.913 Hom.: 21085

Bravo AF: 0.924

Asia WGS AF: 0.940 AC: 3269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs2577261; hg19: chr2-11940787;