chr2-11677893-G-A

Position:

• chr2-11677893-G-A

Variant summary

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

The NM_001261428.3(LPIN1):​c.81+165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,322 control chromosomes in the GnomAD database, including 1,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.093 (1005 hom., cov: 33)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.258

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=-0.84).
• BP6: Variant 2-11677893-G-A is Benign according to our data. Variant chr2-11677893-G-A is described in ClinVar as [Benign]. Clinvar id is 1293184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.81+165G>A		intron_variant			NP_001248357.1
LPIN1	NM_001349207.2	c.81+165G>A		intron_variant			NP_001336136.1
LPIN1	NM_001349208.2	c.81+165G>A		intron_variant			NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.81+165G>A		intron_variant		2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14185 AN: 152204 Hom.: 1004 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0769

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0933 AC: 14209 AN: 152322 Hom.: 1005 Cov.: 33 AF XY: 0.0948 AC XY: 7064 AN XY: 74496

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.0402

Gnomad4 OTH AF: 0.0784

Alfa AF: 0.0722 Hom.: 168

Bravo AF: 0.0968

Asia WGS AF: 0.114 AC: 399 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11694975; hg19: chr2-11818019;