Genetic Variant LBP:p.Leu48Leu (chr20-38349567-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004139.5(LBP):c.144A>G(p.Leu48Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,608,104 control chromosomes in the GnomAD database, including 710,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.90 ( 61637 hom., cov: 31)

Exomes 𝑓: 0.94 ( 648789 hom. )

Consequence

LBP
NM_004139.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.787

Publications

16 publications found

Variant links:

Genes affected

LBP (HGNC:6517): (lipopolysaccharide binding protein) The protein encoded by this gene is involved in the acute-phase immunologic response to gram-negative bacterial infections. Gram-negative bacteria contain a glycolipid, lipopolysaccharide (LPS), on their outer cell wall. Together with bactericidal permeability-increasing protein (BPI), the encoded protein binds LPS and interacts with the CD14 receptor, probably playing a role in regulating LPS-dependent monocyte responses. Studies in mice suggest that the encoded protein is necessary for the rapid acute-phase response to LPS but not for the clearance of LPS from circulation. This protein is part of a family of structurally and functionally related proteins, including BPI, plasma cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP). [provided by RefSeq, Apr 2012]

LBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 20-38349567-A-G is Benign according to our data. Variant chr20-38349567-A-G is described in ClinVar as [Benign]. Clinvar id is 769090.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.787 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.144A>G	p.Leu48Leu	synonymous_variant	Exon 2 of 15	ENST00000217407.3	NP_004130.2	P18428Q8TCF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3 link	c.144A>G	p.Leu48Leu	synonymous_variant	Exon 2 of 15	1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136455

AN:

152028

Hom.:

61600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.801

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.902

Gnomad ASJ

AF:

0.894

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.869

Gnomad FIN

AF:

0.939

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.893

GnomAD4 exome

AF:

0.943

AC:

1373147

AN:

1455958

Hom.:

648789

Cov.:

AF XY:

0.941

AC XY:

681195

AN XY:

723528

show subpopulations

African (AFR)

AF:

0.793

AC:

26478

AN:

33402

American (AMR)

AF:

0.903

AC:

39653

AN:

43924

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

23279

AN:

25972

East Asian (EAS)

AF:

0.849

AC:

33571

AN:

39540

South Asian (SAS)

AF:

0.877

AC:

74423

AN:

84894

European-Finnish (FIN)

AF:

0.941

AC:

49514

AN:

52636

Middle Eastern (MID)

AF:

0.827

AC:

4763

AN:

5758

European-Non Finnish (NFE)

AF:

0.961

AC:

1066228

AN:

1109658

Other (OTH)

AF:

0.918

AC:

55238

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

4208

8416

12625

16833

21041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.897

AC:

136545

AN:

152146

Hom.:

61637

Cov.:

AF XY:

0.896

AC XY:

66691

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.801

AC:

33231

AN:

41488

American (AMR)

AF:

0.902

AC:

13780

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

3103

AN:

3470

East Asian (EAS)

AF:

0.838

AC:

4312

AN:

5144

South Asian (SAS)

AF:

0.870

AC:

4197

AN:

4822

European-Finnish (FIN)

AF:

0.939

AC:

9954

AN:

10604

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.955

AC:

64982

AN:

68024

Other (OTH)

AF:

0.893

AC:

1885

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

663

1326

1990

2653

3316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.933

Hom.:

104106

Bravo

AF:

0.891

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

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

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.4

(source)

PhyloP100

0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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20-38349567-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over