dbSNP rs77960347: LIPG:p.Asn396Ser (chr18-49583585-A-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006033.4(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
NM_006033.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.50

Publications

99 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1169438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPG	NM_006033.4	MANE Select	c.1187A>G	p.Asn396Ser	missense	Exon 8 of 10	NP_006024.1	Q9Y5X9-1
	LIPG	NM_001308006.2		c.965A>G	p.Asn322Ser	missense	Exon 7 of 9	NP_001294935.1	B4DTR8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIPG	ENST00000261292.9	TSL:1 MANE Select	c.1187A>G	p.Asn396Ser	missense	Exon 8 of 10	ENSP00000261292.4	Q9Y5X9-1
LIPG	ENST00000959465.1		c.1178A>G	p.Asn393Ser	missense	Exon 8 of 10	ENSP00000629524.1
LIPG	ENST00000931130.1		c.1007A>G	p.Asn336Ser	missense	Exon 7 of 9	ENSP00000601189.1

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

GnomAD2 exomes

AF:

0.00872

AC:

2192

AN:

251332

AF XY:

0.00897

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 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

African (AFR)

AF:

0.00197

AC:

AN:

33480

American (AMR)

AF:

0.00604

AC:

270

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

286

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00555

AC:

479

AN:

86258

European-Finnish (FIN)

AF:

0.00622

AC:

332

AN:

53412

Middle Eastern (MID)

AF:

0.0166

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0133

AC:

14754

AN:

1111968

Other (OTH)

AF:

0.0115

AC:

696

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

913

1827

2740

3654

4567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

554

1108

1662

2216

2770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00794

AC:

1208

AN:

152202

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

525

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.00267

AC:

111

AN:

41554

American (AMR)

AF:

0.00884

AC:

135

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00374

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00556

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

821

AN:

67992

Other (OTH)

AF:

0.0128

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0115

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.079

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

3.1

PhyloP100

7.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.34

Sift

Benign

0.21

Sift4G

Benign

0.32

Polyphen

1.0

Vest4

0.49

MVP

0.87

MPC

0.80

ClinPred

0.051

GERP RS

5.6

Varity_R

0.13

gMVP

0.74

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over