rs142083008

chr2-11788351-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001349206.2(LPIN1):c.1644-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,528,396 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (3 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-11788351-C-T is Benign according to our data. Variant chr2-11788351-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262584.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0041 (624/152242) while in subpopulation AFR AF= 0.0103 (426/41532). AF 95% confidence interval is 0.00945. There are 2 homozygotes in gnomad4. There are 282 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN1	NM_001349206.2	c.1644-36C>T		intron_variant		ENST00000674199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN1	ENST00000674199.1	c.1644-36C>T		intron_variant			NM_001349206.2	P4

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 617 AN: 152124 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00200 AC: 502 AN: 251272 Hom.: 2 AF XY: 0.00190 AC XY: 258 AN XY: 135820

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.0100

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00129

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00122 AC: 1673 AN: 1376154 Hom.: 3 Cov.: 21 AF XY: 0.00121 AC XY: 838 AN XY: 689938

Gnomad4 AFR exome AF: 0.00981

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.00934

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000296

Gnomad4 FIN exome AF: 0.0000938

Gnomad4 NFE exome AF: 0.000823

Gnomad4 OTH exome AF: 0.00244

GnomAD4 genome AF: 0.00410 AC: 624 AN: 152242 Hom.: 2 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74426

Gnomad4 AFR AF: 0.0103

Gnomad4 AMR AF: 0.00399

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00280 Hom.: 0

Bravo AF: 0.00497

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.055
Dann	Benign	0.78

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: rs142083008; hg19: chr2-11928477;