rs2716609

chr2-11819779-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001349206.2(LPIN1):c.2517+181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,068 control chromosomes in the GnomAD database, including 8,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (8052 hom., cov: 32)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.270

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-11819779-T-C is Benign according to our data. Variant chr2-11819779-T-C is described in ClinVar as [Benign]. Clinvar id is 1295170.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.2517+181T>C		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.2517+181T>C		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40691 AN: 151950 Hom.: 8006 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0913

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.268 AC: 40790 AN: 152068 Hom.: 8052 Cov.: 32 AF XY: 0.263 AC XY: 19582 AN XY: 74352

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.0913

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.240

Alfa AF: 0.190 Hom.: 3690

Bravo AF: 0.293

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.5
Dann	Benign	0.49

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: rs2716609; hg19: chr2-11959905;