Variant 18-49567494-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_006033.4(LIPG):c.332C>T(p.Thr111Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,613,700 control chromosomes in the GnomAD database, including 67,329 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.23 ( 4746 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62583 hom. )

Consequence

LIPG
NM_006033.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.421

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=0.012551069).

BP6

Variant 18-49567494-C-T is Benign according to our data. Variant chr18-49567494-C-T is described in ClinVar as [Benign]. Clinvar id is 1647588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-49567494-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LIPG	NM_006033.4 linkuse as main transcript	c.332C>T	p.Thr111Ile	missense_variant	3/10	ENST00000261292.9
LIPG	NM_001308006.2 linkuse as main transcript	c.332C>T	p.Thr111Ile	missense_variant	3/9
LIPG	XM_047437944.1 linkuse as main transcript	c.440C>T	p.Thr147Ile	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPG	ENST00000261292.9 linkuse as main transcript	c.332C>T	p.Thr111Ile	missense_variant	3/10	1	NM_006033.4	P1	Q9Y5X9-1

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35434

AN:

152006

Hom.:

4752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.216

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.318

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.266

AC:

66755

AN:

251106

Hom.:

9624

AF XY:

0.276

AC XY:

37436

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.288

AC:

421079

AN:

1461576

Hom.:

62583

Cov.:

AF XY:

0.290

AC XY:

211173

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.0939

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.304

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

AF:

0.233

AC:

35410

AN:

152124

Hom.:

4746

Cov.:

AF XY:

0.233

AC XY:

17350

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0989

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.318

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.276

Alfa

AF:

0.288

Hom.:

16951

Bravo

AF:

0.223

TwinsUK

AF:

0.291

AC:

1079

ALSPAC

AF:

0.298

AC:

1149

ESP6500AA

AF:

0.107

AC:

473

ESP6500EA

AF:

0.291

AC:

2506

ExAC

AF:

0.267

AC:

32367

Asia WGS

AF:

0.248

AC:

860

AN:

3478

EpiCase

AF:

0.313

EpiControl

AF:

0.312

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.23

CADD

Benign

2.3

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.52

D;D;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.73

T;T;T;T

MetaRNN

Benign

0.013

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.78

.;N;.;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.4

.;N;N;.

REVEL

Benign

0.20

Sift

Benign

0.070

.;T;D;.

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.0030, 0.0050, 0.0020

.;B;B;B

Vest4

0.14

MPC

0.39

ClinPred

0.0038

GERP RS

-3.6

Varity_R

0.037

gMVP

0.15

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