Variant 18-49583585-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000261292.9(LIPG):c.1187A>G(p.Asn396Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,614,042 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 8 hom., cov: 32)

Exomes 𝑓: 0.012 ( 119 hom. )

Consequence

LIPG
ENST00000261292.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.50

Variant links:

Genes affected

LIPG (HGNC:6623): (lipase G, endothelial type) The protein encoded by this gene has substantial phospholipase activity and may be involved in lipoprotein metabolism and vascular biology. This protein is designated a member of the TG lipase family by its sequence and characteristic lid region which provides substrate specificity for enzymes of the TG lipase family. [provided by RefSeq, Jul 2008]

LIPG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010529816).

BP6

Variant 18-49583585-A-G is Benign according to our data. Variant chr18-49583585-A-G is described in ClinVar as [Benign]. Clinvar id is 1169438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49583585-A-G is described in Lovd as [Benign]. Variant chr18-49583585-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	8/10	ENST00000261292.9	NP_006024.1
LIPG	NM_001308006.2 linkuse as main transcript	c.965A>G	p.Asn322Ser	missense_variant	7/9		NP_001294935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	8/10	1	NM_006033.4	ENSP00000261292	P1	Q9Y5X9-1
LIPG	ENST00000427224.6 linkuse as main transcript	c.965A>G	p.Asn322Ser	missense_variant	7/9	2		ENSP00000387978

Frequencies

GnomAD3 genomes

AF:

0.00795

AC:

1209

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00268

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00885

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00872

AC:

2192

AN:

251332

Hom.:

AF XY:

0.00897

AC XY:

1219

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00561

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00559

Gnomad FIN exome

AF:

0.00541

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0116

AC:

16979

AN:

1461840

Hom.:

119

Cov.:

AF XY:

0.0115

AC XY:

8383

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.00604

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00555

Gnomad4 FIN exome

AF:

0.00622

Gnomad4 NFE exome

AF:

0.0133

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.00794

AC:

1208

AN:

152202

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

525

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00267

Gnomad4 AMR

AF:

0.00884

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.00847

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0114

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00915

AC:

1111

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0116

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

T;D

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.1

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.21

T;T

Sift4G

Benign

0.32

T;T

Polyphen

1.0

D;D

Vest4

0.49

MVP

0.87

MPC

0.80

ClinPred

0.051

GERP RS

5.6

Varity_R

0.13

gMVP

0.74

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