Genetic Variant LPIN2:c.590+4762G>A (chr18-2946293-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375808.2(LPIN2):c.590+4762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,228 control chromosomes in the GnomAD database, including 65,084 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.92 ( 65084 hom., cov: 32)

Exomes 𝑓: 0.97 ( 644315 hom. )

Failed GnomAD Quality Control

Consequence

LPIN2
NM_001375808.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

Publications

16 publications found

Variant links:

Genes affected

LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

LPIN2 links:

ENSG00000293203 (HGNC:):

ENSG00000293203 links:

CHORDC1P4 (HGNC:54688): (CHORDC1 pseudogene 4)

CHORDC1P4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2 link	c.590+4762G>A		intron_variant	Intron 4 of 19	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1 link	c.590+4762G>A		intron_variant	Intron 4 of 19		NM_001375808.2	ENSP00000504857.1		Q92539

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139991

AN:

152110

Hom.:

65039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.772

Gnomad AMI

AF:

0.981

Gnomad AMR

AF:

0.960

Gnomad ASJ

AF:

0.966

Gnomad EAS

AF:

0.995

Gnomad SAS

AF:

0.925

Gnomad FIN

AF:

0.996

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.981

Gnomad OTH

AF:

0.920

GnomAD2 exomes

AF:

0.961

AC:

241337

AN:

251088

AF XY:

0.962

show subpopulations

Gnomad AFR exome

AF:

0.765

Gnomad AMR exome

AF:

0.976

Gnomad ASJ exome

AF:

0.962

Gnomad EAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.996

Gnomad NFE exome

AF:

0.981

Gnomad OTH exome

AF:

0.963

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.973

AC:

1321826

AN:

1358094

Hom.:

644315

Cov.:

AF XY:

0.972

AC XY:

662414

AN XY:

681266

show subpopulations

African (AFR)

AF:

0.761

AC:

23445

AN:

30818

American (AMR)

AF:

0.974

AC:

43459

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.966

AC:

24600

AN:

25474

East Asian (EAS)

AF:

0.997

AC:

39072

AN:

39174

South Asian (SAS)

AF:

0.929

AC:

78068

AN:

84016

European-Finnish (FIN)

AF:

0.996

AC:

53116

AN:

53342

Middle Eastern (MID)

AF:

0.899

AC:

4988

AN:

5550

European-Non Finnish (NFE)

AF:

0.982

AC:

1000460

AN:

1018324

Other (OTH)

AF:

0.962

AC:

54618

AN:

56796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1815

3630

5445

7260

9075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19116

38232

57348

76464

95580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.920

AC:

140096

AN:

152228

Hom.:

65084

Cov.:

AF XY:

0.922

AC XY:

68600

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.772

AC:

32021

AN:

41484

American (AMR)

AF:

0.960

AC:

14686

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.966

AC:

3351

AN:

3470

East Asian (EAS)

AF:

0.995

AC:

5154

AN:

5180

South Asian (SAS)

AF:

0.926

AC:

4467

AN:

4826

European-Finnish (FIN)

AF:

0.996

AC:

10571

AN:

10614

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.981

AC:

66733

AN:

68034

Other (OTH)

AF:

0.921

AC:

1945

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

510

1021

1531

2042

2552

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.965

Hom.:

195334

Bravo

AF:

0.912

Asia WGS

AF:

0.957

AC:

3328

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.7

(source)

DANN

Benign

0.67

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over