chr20-38369011-C-T

Variant names:

• chr20-38369011-C-T
• rs2232613
• NM_004139.5:c.998C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004139.5(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).

• Frequency:
  • Genomes: 𝑓 0.079 (561 hom., cov: 32)
  • Exomes 𝑓: 0.076 (4764 hom.)
• Consequence: LBP NM_004139.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.61
• Publications: 34 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004139.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	NM_004139.5	MANE Select	c.998C>T	p.Pro333Leu	missense	Exon 10 of 15	NP_004130.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.998C>T	p.Pro333Leu	missense	Exon 10 of 15	ENSP00000217407.2
	LBP	ENST00000901257.1		c.1055C>T	p.Pro352Leu	missense	Exon 10 of 15	ENSP00000571316.1
	LBP	ENST00000901253.1		c.989C>T	p.Pro330Leu	missense	Exon 10 of 15	ENSP00000571312.1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12055 AN: 152068 Hom.: 560 Cov.: 32

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

GnomAD2 exomes AF: 0.0657 AC: 16517 AN: 251406 AF XY: 0.0654

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 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.: 33 AF XY: 0.0750 AC XY: 54517 AN XY: 727040

African (AFR) AF: 0.0912 AC: 3051 AN: 33464

American (AMR) AF: 0.0333 AC: 1491 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 884 AN: 26132

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39698

South Asian (SAS) AF: 0.0491 AC: 4238 AN: 86254

European-Finnish (FIN) AF: 0.139 AC: 7401 AN: 53406

Middle Eastern (MID) AF: 0.0192 AC: 111 AN: 5768

European-Non Finnish (NFE) AF: 0.0804 AC: 89406 AN: 1111554

Other (OTH) AF: 0.0735 AC: 4441 AN: 60384

GnomAD4 genome AF: 0.0793 AC: 12069 AN: 152186 Hom.: 561 Cov.: 32 AF XY: 0.0801 AC XY: 5958 AN XY: 74384

African (AFR) AF: 0.0901 AC: 3743 AN: 41534

American (AMR) AF: 0.0549 AC: 838 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0482 AC: 232 AN: 4814

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5462 AN: 68012

Other (OTH) AF: 0.0600 AC: 127 AN: 2116

Alfa AF: 0.0733 Hom.: 1818

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

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-9.5	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.30
MPC		0.49
ClinPred		0.063	T
GERP RS		4.6
Varity_R		0.92
gMVP		0.65
Mutation Taster		=82/18	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2232613; hg19: chr20-36997655; COSMIC: COSV54144300;