Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000681601.1(LIPI):c.164G>A(p.Cys55Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00352 in 1,613,860 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 26 hom. )

Consequence

LIPI
ENST00000681601.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 4.99

Publications

9 publications found

Variant links:

Genes affected

LIPI (HGNC:18821): (lipase I) The protein encoded by this gene is a phospholipase that hydrolyzes phosphatidic acid to produce lysophosphatidic acid. Defects in this gene are a cause of susceptibility to familial hypertrigliceridemia. This gene is also expressed at high levels in Ewing family tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

LIPI Gene-Disease associations (from GenCC):

hypertriglyceridemia
Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp

LIPI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014380097).

BP6

Variant 21-14189302-C-T is Benign according to our data. Variant chr21-14189302-C-T is described in ClinVar as Benign. ClinVar VariationId is 1822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00712 (1084/152256) while in subpopulation AFR AF = 0.0178 (738/41560). AF 95% confidence interval is 0.0167. There are 11 homozygotes in GnomAd4. There are 527 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1084 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000681601.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LIPI	NM_001302998.2	MANE Select	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 10	NP_001289927.1
LIPI	NM_001303000.2		c.164G>A	p.Cys55Tyr	missense	Exon 2 of 10	NP_001289929.1
LIPI	NM_001302999.2		c.164G>A	p.Cys55Tyr	missense	Exon 2 of 9	NP_001289928.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LIPI	ENST00000681601.1	MANE Select	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 10	ENSP00000505323.1
LIPI	ENST00000536861.6	TSL:1	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 10	ENSP00000440381.3
LIPI	ENST00000614229.5	TSL:1	c.164G>A	p.Cys55Tyr	missense	Exon 2 of 9	ENSP00000482652.2

Frequencies

GnomAD3 genomes

AF:

0.00712

AC:

1083

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00472

AC:

1187

AN:

251350

AF XY:

0.00468

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.0173

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.00315

AC:

4602

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

2367

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.0224

AC:

749

AN:

33470

American (AMR)

AF:

0.00400

AC:

179

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

447

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00698

AC:

602

AN:

86250

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00203

AC:

2262

AN:

1111794

Other (OTH)

AF:

0.00494

AC:

298

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

239

477

716

954

1193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.00712

AC:

1084

AN:

152256

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0178

AC:

738

AN:

41560

American (AMR)

AF:

0.00477

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00373

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00244

AC:

166

AN:

68018

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00440

Hom.:

Bravo

AF:

0.00804

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.0191

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00492

AC:

597

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00379

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hypertriglyceridemia 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

MetaRNN

Benign

0.014

MetaSVM

Uncertain

0.45

PhyloP100

5.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-11

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MVP

0.79

MPC

0.16

ClinPred

0.062

GERP RS

5.3

gMVP

0.70

Mutation Taster

=69/31

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11909217

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over