20-38354288-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004139.5(LBP):c.373C>A(p.Leu125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,612,580 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 66 hom. )

Consequence

LBP
NM_004139.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.927

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025353432).

BP6

Variant 20-38354288-C-A is Benign according to our data. Variant chr20-38354288-C-A is described in ClinVar as [Benign]. Clinvar id is 771532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00495 (754/152308) while in subpopulation AMR AF= 0.0301 (461/15302). AF 95% confidence interval is 0.0279. There are 7 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.373C>A	p.Leu125Ile	missense_variant	Exon 4 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.373C>A	p.Leu125Ile	missense_variant	Exon 4 of 15	1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

750

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0299

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00788

AC:

1971

AN:

249978

Hom.:

AF XY:

0.00643

AC XY:

869

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.0394

Gnomad ASJ exome

AF:

0.00531

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.00680

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00739

GnomAD4 exome

AF:

0.00378

AC:

5524

AN:

1460272

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

2532

AN XY:

726436

show subpopulations

Gnomad4 AFR exome

AF:

0.000419

Gnomad4 AMR exome

AF:

0.0403

Gnomad4 ASJ exome

AF:

0.00526

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000581

Gnomad4 FIN exome

AF:

0.00716

Gnomad4 NFE exome

AF:

0.00253

Gnomad4 OTH exome

AF:

0.00446

GnomAD4 genome

AF:

0.00495

AC:

754

AN:

152308

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.0301

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00613

Gnomad4 NFE

AF:

0.00240

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00577

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00635

AC:

771

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00243

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.0

DANN

Benign

0.95

DEOGEN2

Benign

0.039

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.28

REVEL

Benign

0.10

Sift

Benign

0.23

Sift4G

Benign

0.18

Polyphen

0.12

Vest4

0.36

MVP

0.17

MPC

0.36

ClinPred

0.012

GERP RS

2.8

Varity_R

0.22

gMVP

0.24

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