2-11713717-C-T

Variant summary

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

The NM_001261428.3(LPIN1):c.82-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 1,251,100 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (36 hom., cov: 33)
  • Exomes 𝑓: 0.012 (156 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

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=-0.81).
• BP6: Variant 2-11713717-C-T is Benign according to our data. Variant chr2-11713717-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1193983.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0187 (2845/152256) while in subpopulation AFR AF= 0.0384 (1595/41544). AF 95% confidence interval is 0.0368. There are 36 homozygotes in gnomad4. There are 1421 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 38 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001261428.3	c.82-39C>T		intron_variant
LPIN1	NM_001349207.2	c.81+35989C>T		intron_variant
LPIN1	NM_001349208.2	c.82-39C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000449576.6	c.82-39C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2847 AN: 152138 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0150 AC: 1801 AN: 119892 Hom.: 29 AF XY: 0.0160 AC XY: 1046 AN XY: 65448

Gnomad AFR exome AF: 0.0403

Gnomad AMR exome AF: 0.00973

Gnomad ASJ exome AF: 0.00958

Gnomad EAS exome AF: 0.000986

Gnomad SAS exome AF: 0.0322

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.0177

GnomAD4 exome AF: 0.0119 AC: 13048 AN: 1098844 Hom.: 156 Cov.: 15 AF XY: 0.0125 AC XY: 6901 AN XY: 553182

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.0106

Gnomad4 ASJ exome AF: 0.00996

Gnomad4 EAS exome AF: 0.000521

Gnomad4 SAS exome AF: 0.0316

Gnomad4 FIN exome AF: 0.00890

Gnomad4 NFE exome AF: 0.00970

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0187 AC: 2845 AN: 152256 Hom.: 36 Cov.: 33 AF XY: 0.0191 AC XY: 1421 AN XY: 74438

Gnomad4 AFR AF: 0.0384

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0132 Hom.: 8

Bravo AF: 0.0195

Asia WGS AF: 0.0320 AC: 112 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

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	5.9
Dann	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58166101; hg19: chr2-11853843;