rs893346

Positions:

• chr2-11742635-A-G

Variant summary

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

The ENST00000396098.5(LPIN1):​c.9+1207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,130 control chromosomes in the GnomAD database, including 7,714 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 0.22 (7714 hom., cov: 33)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124907735	XR_007086220.1	n.1632+1193T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000431500.2	n.136-479T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32869 AN: 152012 Hom.: 7695 Cov.: 33

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.217 AC: 32946 AN: 152130 Hom.: 7714 Cov.: 33 AF XY: 0.211 AC XY: 15691 AN XY: 74380

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.0715

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0900 Hom.: 1845

Bravo AF: 0.235

Asia WGS AF: 0.0860 AC: 300 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	0.10
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs893346; hg19: chr2-11882761;