chr2-11741072-A-C

Position:

• chr2-11741072-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000396098.5(LPIN1):​c.-71-277A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 275,402 control chromosomes in the GnomAD database, including 11,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (9243 hom., cov: 33)
  • Exomes 𝑓: 0.17 (2417 hom.)
• Consequence: LPIN1 ENST00000396098.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.292

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-11741072-A-C is Benign according to our data. Variant chr2-11741072-A-C is described in ClinVar as [Benign]. Clinvar id is 684294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124907735	XR_007086220.1	n.1863T>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000431500.2	n.486T>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43073 AN: 152052 Hom.: 9227 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.170 AC: 20903 AN: 123232 Hom.: 2417 Cov.: 0 AF XY: 0.168 AC XY: 10428 AN XY: 61940

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.00225

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.284 AC: 43141 AN: 152170 Hom.: 9243 Cov.: 33 AF XY: 0.277 AC XY: 20645 AN XY: 74412

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0843

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.234

Alfa AF: 0.293 Hom.: 1343

Bravo AF: 0.298

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56788115; hg19: chr2-11881198;