Variant rs11909217 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001302998.2(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
NM_001302998.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.99

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:

LIPI (HGNC:):

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=0.014380097).

BP6

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

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1084 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPI	NM_001302998.2 linkuse as main transcript	c.164G>A	p.Cys55Tyr	missense_variant	2/10	ENST00000681601.1	NP_001289927.1	Q6XZB0-1Q5D1Q2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPI	ENST00000681601.1 linkuse as main transcript	c.164G>A	p.Cys55Tyr	missense_variant	2/10		NM_001302998.2	ENSP00000505323.1		Q6XZB0-1

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

GnomAD3 exomes

AF:

0.00472

AC:

1187

AN:

251350

Hom.:

AF XY:

0.00468

AC XY:

636

AN XY:

135852

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 SAS exome

AF:

0.00706

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

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00698

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.00712

AC:

1084

AN:

152256

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00244

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00441

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

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

Hypertriglyceridemia 1

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

May 15, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

0.45

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-11

D;.;.

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.92

MVP

0.79

MPC

0.16

ClinPred

0.062

GERP RS

5.3

gMVP

0.70

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