chr2-11677857-G-T

Position:

• chr2-11677857-G-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.81+129G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00783 in 757,330 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0062 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (41 hom.)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400

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=-0.89).
• BP6: Variant 2-11677857-G-T is Benign according to our data. Variant chr2-11677857-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1195378.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0062 (945/152386) while in subpopulation NFE AF= 0.0106 (718/68034). AF 95% confidence interval is 0.00991. There are 6 homozygotes in gnomad4. There are 439 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.81+129G>T		intron_variant			NP_001248357.1
LPIN1	NM_001349207.2	c.81+129G>T		intron_variant			NP_001336136.1
LPIN1	NM_001349208.2	c.81+129G>T		intron_variant			NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.81+129G>T		intron_variant		2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes AF: 0.00621 AC: 946 AN: 152268 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00825 AC: 4988 AN: 604944 Hom.: 41 AF XY: 0.00809 AC XY: 2544 AN XY: 314620

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00615

Gnomad4 ASJ exome AF: 0.00254

Gnomad4 EAS exome AF: 0.0000313

Gnomad4 SAS exome AF: 0.000533

Gnomad4 FIN exome AF: 0.00489

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.00717

GnomAD4 genome AF: 0.00620 AC: 945 AN: 152386 Hom.: 6 Cov.: 33 AF XY: 0.00589 AC XY: 439 AN XY: 74524

Gnomad4 AFR AF: 0.00175

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00926 Hom.: 1

Bravo AF: 0.00661

Asia WGS AF: 0.000289 AC: 1 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 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs144852118; hg19: chr2-11817983;