rs2232618

Positions:

• chr20-38373117-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004139.5(LBP):​c.1306T>C​(p.Phe436Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 1,612,544 control chromosomes in the GnomAD database, including 8,096 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.12 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6830 hom.)
• Consequence: LBP NM_004139.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021943927).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBP	NM_004139.5	c.1306T>C	p.Phe436Leu	missense_variant	13/15	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.1306T>C	p.Phe436Leu	missense_variant	13/15	1	NM_004139.5	ENSP00000217407	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17709 AN: 152058 Hom.: 1259 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.0893

GnomAD3 exomes AF: 0.0923 AC: 23217 AN: 251434 Hom.: 1343 AF XY: 0.0961 AC XY: 13057 AN XY: 135892

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.0471

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.0674

Gnomad NFE exome AF: 0.0895

Gnomad OTH exome AF: 0.0867

GnomAD4 exome AF: 0.0914 AC: 133405 AN: 1460366 Hom.: 6830 Cov.: 30 AF XY: 0.0932 AC XY: 67713 AN XY: 726556

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.0437

Gnomad4 ASJ exome AF: 0.0915

Gnomad4 EAS exome AF: 0.0364

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0686

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.0938

GnomAD4 genome AF: 0.117 AC: 17745 AN: 152178 Hom.: 1266 Cov.: 32 AF XY: 0.116 AC XY: 8626 AN XY: 74392

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0693

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0882

Gnomad4 OTH AF: 0.0917

Alfa AF: 0.0930 Hom.: 1750

Bravo AF: 0.117

TwinsUK AF: 0.0758 AC: 281

ALSPAC AF: 0.0843 AC: 325

ESP6500AA AF: 0.191 AC: 843

ESP6500EA AF: 0.0900 AC: 774

ExAC AF: 0.0964 AC: 11709

Asia WGS AF: 0.106 AC: 366 AN: 3478

EpiCase AF: 0.0964

EpiControl AF: 0.0906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.23
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.015
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0090
MutPred		0.26		Loss of stability (P = 0.07);
MPC		0.11
ClinPred		0.0012	T
GERP RS		-1.0
Varity_R		0.052
gMVP		0.27

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

Other links and lift over

dbSNP: rs2232618; hg19: chr20-37001761; COSMIC: COSV54143579;