Variant rs5744204 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004139.5(LBP):c.496G>A(p.Val166Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,612,810 control chromosomes in the GnomAD database, including 4,522 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.11 ( 2279 hom., cov: 31)

Exomes 𝑓: 0.021 ( 2243 hom. )

Consequence

LBP
NM_004139.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

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=0.0058196783).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.496G>A	p.Val166Met	missense_variant	4/15	ENST00000217407.3	NP_004130.2	P18428Q8TCF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3 link	c.496G>A	p.Val166Met	missense_variant	4/15	1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15940

AN:

152024

Hom.:

2269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0672

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.00783

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0886

GnomAD3 exomes

AF:

0.0372

AC:

9302

AN:

249960

Hom.:

981

AF XY:

0.0315

AC XY:

4260

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0239

Gnomad FIN exome

AF:

0.00995

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0206

AC:

30090

AN:

1460668

Hom.:

2243

Cov.:

AF XY:

0.0201

AC XY:

14591

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.336

Gnomad4 AMR exome

AF:

0.0346

Gnomad4 ASJ exome

AF:

0.0279

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.00966

Gnomad4 OTH exome

AF:

0.0386

GnomAD4 genome

AF:

0.105

AC:

15978

AN:

152142

Hom.:

2279

Cov.:

AF XY:

0.103

AC XY:

7659

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.326

Gnomad4 AMR

AF:

0.0670

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0255

Gnomad4 FIN

AF:

0.00783

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.0877

Alfa

AF:

0.0364

Hom.:

528

Bravo

AF:

0.117

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.313

AC:

1379

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0424

AC:

5145

Asia WGS

AF:

0.0400

AC:

141

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.2

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.046

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.16

MPC

0.42

ClinPred

0.060

GERP RS

0.43

Varity_R

0.20

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over