20-38349646-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004139.5(LBP):c.223C>T(p.Arg75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000311 in 1,605,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

LBP
NM_004139.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.406

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.223C>T	p.Arg75Cys	missense_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.223C>T	p.Arg75Cys	missense_variant	Exon 2 of 15	1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152152

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

234760

AF XY:

0.0000236

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1453092

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

722000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.0000228

AC:

AN:

43812

Ashkenazi Jewish (ASJ)

AF:

0.0000386

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39478

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52480

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

1107706

Other (OTH)

AF:

0.0000500

AC:

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.223C>T (p.R75C) alteration is located in exon 2 (coding exon 2) of the LBP gene. This alteration results from a C to T substitution at nucleotide position 223, causing the arginine (R) at amino acid position 75 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.58

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

-0.41

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.088

Sift

Benign

0.036

Sift4G

Uncertain

0.041

Polyphen

0.97

Vest4

0.22

MutPred

0.59

Loss of methylation at R75 (P = 0.0204);

MVP

0.26

MPC

0.40

ClinPred

0.94

GERP RS

-1.5

Varity_R

0.23

gMVP

0.38

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-38349646-C-T

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