chr2-11713471-A-G

Position:

• chr2-11713471-A-G

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.82-285A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 152,298 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0053 (4 hom., cov: 33)
• Consequence: LPIN1 NM_001261428.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

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=-0.94).
• BP6: Variant 2-11713471-A-G is Benign according to our data. Variant chr2-11713471-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1205038.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0053 (807/152298) while in subpopulation NFE AF= 0.00742 (505/68030). AF 95% confidence interval is 0.00689. There are 4 homozygotes in gnomad4. There are 427 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPIN1	NM_001261428.3	c.82-285A>G		intron_variant			NP_001248357.1
LPIN1	NM_001349207.2	c.81+35743A>G		intron_variant			NP_001336136.1
LPIN1	NM_001349208.2	c.82-285A>G		intron_variant			NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6	c.82-285A>G		intron_variant		2		ENSP00000397908	A2

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 807 AN: 152180 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0170

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.00907

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

GnomAD4 genome AF: 0.00530 AC: 807 AN: 152298 Hom.: 4 Cov.: 33 AF XY: 0.00573 AC XY: 427 AN XY: 74462

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0170

Gnomad4 NFE AF: 0.00742

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00635 Hom.: 0

Bravo AF: 0.00362

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

Mar 15, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.0
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs138163577; hg19: chr2-11853597;