Variant 18-49565334-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_006033.4(LIPG):c.115A>C(p.Lys39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,124 control chromosomes in the GnomAD database, including 30 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 (★).

Frequency

Genomes: 𝑓 0.00076 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

LIPG
NM_006033.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.320

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004745811).

BP6

Variant 18-49565334-A-C is Benign according to our data. Variant chr18-49565334-A-C is described in ClinVar as [Benign]. Clinvar id is 1535219.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-49565334-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000762 (116/152280) while in subpopulation SAS AF= 0.0236 (114/4832). AF 95% confidence interval is 0.0201. There are 2 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPG	NM_006033.4 linkuse as main transcript	c.115A>C	p.Lys39Gln	missense_variant	2/10	ENST00000261292.9	NP_006024.1	Q9Y5X9-1A0A024R2B5
LIPG	NM_001308006.2 linkuse as main transcript	c.115A>C	p.Lys39Gln	missense_variant	2/9		NP_001294935.1	Q9Y5X9B4DTR8
LIPG	XM_047437944.1 linkuse as main transcript	c.223A>C	p.Lys75Gln	missense_variant	2/5		XP_047293900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPG	ENST00000261292.9 linkuse as main transcript	c.115A>C	p.Lys39Gln	missense_variant	2/10	1	NM_006033.4	ENSP00000261292.4		Q9Y5X9-1

Frequencies

GnomAD3 genomes

AF:

0.000762

AC:

116

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0236

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00218

AC:

548

AN:

251322

Hom.:

AF XY:

0.00277

AC XY:

377

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0175

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00109

AC:

1595

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1091

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.000762

AC:

116

AN:

152280

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000831

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.00247

AC:

300

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

1.6

DANN

Benign

0.60

DEOGEN2

Benign

0.0075

T;T;T;.

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.66

T;T;T;T

MetaRNN

Benign

0.0047

T;T;T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.34

.;N;.;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.080

.;N;N;.

REVEL

Benign

0.26

Sift

Benign

0.26

.;T;T;.

Sift4G

Benign

0.33

T;T;T;T

Polyphen

0.096, 0.17, 0.20

.;B;B;B

Vest4

0.38

MVP

0.95

MPC

0.44

ClinPred

0.023

GERP RS

4.2

Varity_R

0.11

gMVP

0.24

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