18-49562384-G-A

Variant names:

Variant summary

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

The NM_006033.4(LIPG):c.76G>A(p.Gly26Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,613,942 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 44 hom. )

Consequence

LIPG
NM_006033.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.63

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027477443).

BP6

Variant 18-49562384-G-A is Benign according to our data. Variant chr18-49562384-G-A is described in ClinVar as [Benign]. Clinvar id is 1169605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49562384-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0143 (2177/152220) while in subpopulation AFR AF= 0.0505 (2095/41516). AF 95% confidence interval is 0.0487. There are 60 homozygotes in gnomad4. There are 987 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPG	NM_006033.4 link	c.76G>A	p.Gly26Ser	missense_variant	Exon 1 of 10	ENST00000261292.9	NP_006024.1	Q9Y5X9-1A0A024R2B5
LIPG	NM_001308006.2 link	c.76G>A	p.Gly26Ser	missense_variant	Exon 1 of 9		NP_001294935.1	Q9Y5X9B4DTR8
LIPG	XM_047437944.1 link	c.205+494G>A		intron_variant	Intron 1 of 4		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9 link	c.76G>A	p.Gly26Ser	missense_variant	Exon 1 of 10	1	NM_006033.4	ENSP00000261292.4		Q9Y5X9-1

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2178

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.00365

AC:

909

AN:

249286

Hom.:

AF XY:

0.00255

AC XY:

344

AN XY:

134928

show subpopulations

Gnomad AFR exome

AF:

0.0522

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000717

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00141

AC:

2057

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

883

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0507

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.0143

AC:

2177

AN:

152220

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

987

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00272

Hom.:

Bravo

AF:

0.0163

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0463

AC:

204

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00478

AC:

580

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.051

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

L;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

0.34

N;N;.

REVEL

Benign

0.24

Sift

Benign

0.26

T;T;.

Sift4G

Benign

0.49

T;T;T

Polyphen

0.029

B;B;B

Vest4

0.075

MVP

0.91

MPC

0.36

ClinPred

0.0058

GERP RS

2.4

Varity_R

0.077

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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