chr20-38354411-G-A

Position:

• chr20-38354411-G-A

Variant summary

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

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.11 (2279 hom., cov: 31)
  • Exomes 𝑓: 0.021 (2243 hom.)
• Consequence: LBP NM_004139.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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=0.0058196783).
• 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	c.496G>A	p.Val166Met	missense_variant	4/15	ENST00000217407.3	NP_004130.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15940 AN: 152024 Hom.: 2269 Cov.: 31

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

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.: 31 AF XY: 0.0201 AC XY: 14591 AN XY: 726620

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.: 31 AF XY: 0.103 AC XY: 7659 AN XY: 74394

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: 33

ALSPAC AF: 0.00701 AC: 27

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	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.16
MPC		0.42
ClinPred		0.060	T
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

Other links and lift over

dbSNP: rs5744204; hg19: chr20-36982811; COSMIC: COSV54142257;