Variant chr20-38369011-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000217407.3(LBP):c.998C>T(p.Pro333Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0763 in 1,613,568 control chromosomes in the GnomAD database, including 5,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.079 ( 561 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4764 hom. )

Consequence

LBP
ENST00000217407.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 4.61

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028777719).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBP	NM_004139.5 linkuse as main transcript	c.998C>T	p.Pro333Leu	missense_variant	10/15	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3 linkuse as main transcript	c.998C>T	p.Pro333Leu	missense_variant	10/15	1	NM_004139.5	ENSP00000217407	P1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12055

AN:

152068

Hom.:

560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0901

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0550

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0473

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.0606

GnomAD3 exomes

AF:

0.0657

AC:

16517

AN:

251406

Hom.:

731

AF XY:

0.0654

AC XY:

8889

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0916

Gnomad AMR exome

AF:

0.0319

Gnomad ASJ exome

AF:

0.0309

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.0494

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.0759

Gnomad OTH exome

AF:

0.0688

GnomAD4 exome

AF:

0.0760

AC:

111036

AN:

1461382

Hom.:

4764

Cov.:

AF XY:

0.0750

AC XY:

54517

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0912

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.0338

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0491

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.0804

Gnomad4 OTH exome

AF:

0.0735

GnomAD4 genome

AF:

0.0793

AC:

12069

AN:

152186

Hom.:

561

Cov.:

AF XY:

0.0801

AC XY:

5958

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0901

Gnomad4 AMR

AF:

0.0549

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0482

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.0803

Gnomad4 OTH

AF:

0.0600

Alfa

AF:

0.0716

Hom.:

921

Bravo

AF:

0.0715

TwinsUK

AF:

0.0860

AC:

319

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.0960

AC:

423

ESP6500EA

AF:

0.0801

AC:

689

ExAC

AF:

0.0653

AC:

7923

Asia WGS

AF:

0.0300

AC:

105

AN:

3478

EpiCase

AF:

0.0737

EpiControl

AF:

0.0657

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Oct 17, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0029

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

0.0000025

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-9.5

REVEL

Benign

0.26

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.30

MPC

0.49

ClinPred

0.063

GERP RS

4.6

Varity_R

0.92

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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