2-11744990-G-A

Position:

• chr2-11744990-G-A

Variant summary

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

The ENST00000396098.5(LPIN1):​c.9+3562G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,156 control chromosomes in the GnomAD database, including 11,801 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 0.37 (11801 hom., cov: 33)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

LOC124907735 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124907735	XR_007086220.1	n.470C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000431500.2	n.135+177C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56680 AN: 152036 Hom.: 11802 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.373 AC: 56695 AN: 152156 Hom.: 11801 Cov.: 33 AF XY: 0.369 AC XY: 27427 AN XY: 74376

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.402

Alfa AF: 0.386 Hom.: 3601

Bravo AF: 0.361

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs893345; hg19: chr2-11885116;