Variant 21-14109044-G-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.1332C>A(p.Asp444Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,593,002 control chromosomes in the GnomAD database, including 202,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict 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 0.51 ( 19642 hom., cov: 32)

Exomes 𝑓: 0.50 ( 183083 hom. )

Consequence

LIPI
NM_001302998.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.208

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:

(HGNC:):

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=5.8838337E-5).

BP6

Variant 21-14109044-G-T is Benign according to our data. Variant chr21-14109044-G-T is described in ClinVar as [Benign]. Clinvar id is 1600119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.521 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.1332C>A	p.Asp444Glu	missense_variant	10/10	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.1332C>A	p.Asp444Glu	missense_variant	10/10		NM_001302998.2	ENSP00000505323	P4	Q6XZB0-1
	ENST00000428809.5 linkuse as main transcript	n.372+24900G>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77080

AN:

151660

Hom.:

19595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.507

GnomAD3 exomes

AF:

0.502

AC:

125854

AN:

250826

Hom.:

31851

AF XY:

0.501

AC XY:

67931

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.492

Gnomad ASJ exome

AF:

0.449

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.531

Gnomad FIN exome

AF:

0.521

Gnomad NFE exome

AF:

0.496

Gnomad OTH exome

AF:

0.486

GnomAD4 exome

AF:

0.503

AC:

724318

AN:

1441222

Hom.:

183083

Cov.:

AF XY:

0.502

AC XY:

360697

AN XY:

718344

show subpopulations

Gnomad4 AFR exome

AF:

0.500

Gnomad4 AMR exome

AF:

0.494

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.493

Gnomad4 SAS exome

AF:

0.523

Gnomad4 FIN exome

AF:

0.515

Gnomad4 NFE exome

AF:

0.504

Gnomad4 OTH exome

AF:

0.494

GnomAD4 genome

AF:

0.508

AC:

77179

AN:

151780

Hom.:

19642

Cov.:

AF XY:

0.509

AC XY:

37740

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.531

Gnomad4 ASJ

AF:

0.440

Gnomad4 EAS

AF:

0.499

Gnomad4 SAS

AF:

0.521

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.503

Gnomad4 OTH

AF:

0.513

Alfa

AF:

0.498

Hom.:

43927

Bravo

AF:

0.505

TwinsUK

AF:

0.500

AC:

1855

ALSPAC

AF:

0.523

AC:

2017

ESP6500AA

AF:

0.508

AC:

2238

ESP6500EA

AF:

0.494

AC:

4250

ExAC

AF:

0.501

AC:

60797

Asia WGS

AF:

0.550

AC:

1913

AN:

3474

EpiCase

AF:

0.485

EpiControl

AF:

0.488

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	Feb 01, 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

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.5

DANN

Benign

0.70

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.19

T;T;T

MetaRNN

Benign

0.000059

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

2.2

N;.;.

REVEL

Benign

0.23

Sift

Benign

1.0

T;.;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.049

MutPred

0.43

Gain of sheet (P = 0.0125);.;.;

MPC

0.017

ClinPred

0.0020

GERP RS

0.13

gMVP

0.23

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

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