Genetic Variant NM_001261428.3:c.81+9C>T (chr2-11677737-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001261428.3(LPIN1):c.81+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,534,882 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 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

LPIN1
NM_001261428.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.946

Variant links:

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]

LPIN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-11677737-C-T is Benign according to our data. Variant chr2-11677737-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3766514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0011 (167/152386) while in subpopulation SAS AF= 0.00248 (12/4834). AF 95% confidence interval is 0.00144. There are 0 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
LPIN1	NM_001261428.3 link	c.81+9C>T	intron_variant	Intron 1 of 21	NP_001248357.1	Q14693-7
LPIN1	NM_001349207.2 link	c.81+9C>T	intron_variant	Intron 1 of 20	NP_001336136.1
LPIN1	NM_001349208.2 link	c.81+9C>T	intron_variant	Intron 1 of 20	NP_001336137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000449576.6 link	c.81+9C>T		intron_variant	Intron 1 of 21	2		ENSP00000397908.2		Q14693-7

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

167

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00169

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000787

AC:

101

AN:

128284

Hom.:

AF XY:

0.000926

AC XY:

AN XY:

70230

show subpopulations

Gnomad AFR exome

AF:

0.000328

Gnomad AMR exome

AF:

0.0000821

Gnomad ASJ exome

AF:

0.00124

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000946

Gnomad OTH exome

AF:

0.000251

GnomAD4 exome

AF:

0.00134

AC:

1849

AN:

1382496

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

935

AN XY:

682190

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.000953

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.0000896

Gnomad4 NFE exome

AF:

0.00151

Gnomad4 OTH exome

AF:

0.000674

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152386

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00169

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00102

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myoglobinuria, acute recurrent, autosomal recessive

Benign:1

Mar 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.82

DANN

Benign

0.86

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over