Variant 21-14144627-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.1291G>A(p.Glu431Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,489,842 control chromosomes in the GnomAD database, including 84,235 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 0.38 ( 12009 hom., cov: 32)

Exomes 𝑓: 0.32 ( 72226 hom. )

Consequence

LIPI
NM_001302998.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.08

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=0.0019997656).

BP6

Variant 21-14144627-C-T is Benign according to our data. Variant chr21-14144627-C-T is described in ClinVar as [Benign]. Clinvar id is 1600660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 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.1291G>A	p.Glu431Lys	missense_variant	9/10	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.1291G>A	p.Glu431Lys	missense_variant	9/10		NM_001302998.2	ENSP00000505323	P4	Q6XZB0-1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57825

AN:

151702

Hom.:

11988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.266

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.340

Gnomad OTH

AF:

0.375

GnomAD3 exomes

AF:

0.309

AC:

75681

AN:

244690

Hom.:

13173

AF XY:

0.307

AC XY:

40544

AN XY:

132206

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.280

Gnomad ASJ exome

AF:

0.374

Gnomad EAS exome

AF:

0.0486

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.336

GnomAD4 exome

AF:

0.319

AC:

426515

AN:

1338026

Hom.:

72226

Cov.:

AF XY:

0.316

AC XY:

211234

AN XY:

668236

show subpopulations

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.292

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.0563

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.381

AC:

57890

AN:

151816

Hom.:

12009

Cov.:

AF XY:

0.374

AC XY:

27765

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.543

Gnomad4 AMR

AF:

0.344

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.0531

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.314

Gnomad4 NFE

AF:

0.340

Gnomad4 OTH

AF:

0.371

Alfa

AF:

0.348

Hom.:

11487

Bravo

AF:

0.392

TwinsUK

AF:

0.340

AC:

1261

ALSPAC

AF:

0.337

AC:

1297

ESP6500AA

AF:

0.533

AC:

2345

ESP6500EA

AF:

0.338

AC:

2904

ExAC

AF:

0.318

AC:

38621

Asia WGS

AF:

0.161

AC:

560

AN:

3470

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

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.078

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.86

D;D;D

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

0.93

P;P

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.8

D;.;.

REVEL

Uncertain

0.29

Sift

Benign

0.066

T;.;.

Sift4G

Benign

0.13

T;T;T

Polyphen

0.32

B;.;.

Vest4

0.16

MPC

0.13

ClinPred

0.030

GERP RS

5.3

gMVP

0.54

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