rs17603350

chr2-11788297-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001349206.2(LPIN1):c.1644-90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 992,702 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (62 hom., cov: 32)
  • Exomes 𝑓: 0.030 (518 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35

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=-0.93).
• BP6: Variant 2-11788297-C-T is Benign according to our data. Variant chr2-11788297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1187503.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-11788297-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3776/152248) while in subpopulation NFE AF= 0.0399 (2713/68020). AF 95% confidence interval is 0.0386. There are 62 homozygotes in gnomad4. There are 1744 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.1644-90C>T		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.1644-90C>T		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3776 AN: 152130 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0399

Gnomad OTH AF: 0.0321

GnomAD4 exome AF: 0.0304 AC: 25508 AN: 840454 Hom.: 518 AF XY: 0.0296 AC XY: 13087 AN XY: 442662

Gnomad4 AFR exome AF: 0.00661

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.0000278

Gnomad4 SAS exome AF: 0.00748

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0390

Gnomad4 OTH exome AF: 0.0313

GnomAD4 genome AF: 0.0248 AC: 3776 AN: 152248 Hom.: 62 Cov.: 32 AF XY: 0.0234 AC XY: 1744 AN XY: 74444

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0399

Gnomad4 OTH AF: 0.0318

Alfa AF: 0.0318 Hom.: 9

Bravo AF: 0.0254

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.055
Dann	Benign	0.69

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: rs17603350; hg19: chr2-11928423;