Variant 21-14152600-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001302998.2(LIPI):c.1091G>A(p.Gly364Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 1,581,204 control chromosomes in the GnomAD database, including 3,524 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.040 ( 338 hom., cov: 32)

Exomes 𝑓: 0.038 ( 3186 hom. )

Consequence

LIPI
NM_001302998.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.15

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005080998).

BP6

Variant 21-14152600-C-T is Benign according to our data. Variant chr21-14152600-C-T is described in ClinVar as [Benign]. Clinvar id is 1631719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPI	NM_001302998.2 linkuse as main transcript	c.1091G>A	p.Gly364Glu	missense_variant	8/10	ENST00000681601.1	NP_001289927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPI	ENST00000681601.1 linkuse as main transcript	c.1091G>A	p.Gly364Glu	missense_variant	8/10		NM_001302998.2	ENSP00000505323	P4	Q6XZB0-1

Frequencies

GnomAD3 genomes

AF:

0.0397

AC:

6033

AN:

151928

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00856

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.111

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0234

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0690

AC:

17120

AN:

248060

Hom.:

1444

AF XY:

0.0647

AC XY:

8683

AN XY:

134254

show subpopulations

Gnomad AFR exome

AF:

0.00840

Gnomad AMR exome

AF:

0.172

Gnomad ASJ exome

AF:

0.00731

Gnomad EAS exome

AF:

0.274

Gnomad SAS exome

AF:

0.0863

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0213

Gnomad OTH exome

AF:

0.0489

GnomAD4 exome

AF:

0.0377

AC:

53815

AN:

1429158

Hom.:

3186

Cov.:

AF XY:

0.0383

AC XY:

27274

AN XY:

712778

show subpopulations

Gnomad4 AFR exome

AF:

0.00741

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.00723

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.0857

Gnomad4 FIN exome

AF:

0.0388

Gnomad4 NFE exome

AF:

0.0213

Gnomad4 OTH exome

AF:

0.0405

GnomAD4 genome

AF:

0.0397

AC:

6041

AN:

152046

Hom.:

338

Cov.:

AF XY:

0.0438

AC XY:

3257

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00856

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.0379

Gnomad4 NFE

AF:

0.0234

Gnomad4 OTH

AF:

0.0426

Alfa

AF:

0.0334

Hom.:

476

Bravo

AF:

0.0432

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0208

AC:

ESP6500AA

AF:

0.00706

AC:

ESP6500EA

AF:

0.0194

AC:

165

ExAC

AF:

0.0630

AC:

7634

Asia WGS

AF:

0.178

AC:

614

AN:

3452

EpiCase

AF:

0.0200

EpiControl

AF:

0.0197

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0051

T;T;T

MetaSVM

Benign

-1.3

MutationTaster

Benign

0.99

P;P

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

D;.;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0030

D;.;.

Sift4G

Uncertain

0.013

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.22

MPC

0.14

ClinPred

0.018

GERP RS

5.2

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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