rs5744204

Variant names:

• chr20-38354411-G-A
• rs5744204
• NM_004139.5:c.496G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-38354411-G-A
• chr20-38354411-G-C

Variant summary

Our verdict is Benign. The variant received -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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 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=0.0058196783).
• 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 rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.496G>A	p.Val166Met	missense_variant	Exon 4 of 15	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.496G>A	p.Val166Met	missense_variant	Exon 4 of 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

GnomAD2 exomes AF: 0.0372 AC: 9302 AN: 249960 AF XY: 0.0315

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 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

African (AFR) AF: 0.336 AC: 11241 AN: 33446

American (AMR) AF: 0.0346 AC: 1544 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 728 AN: 26112

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39678

South Asian (SAS) AF: 0.0259 AC: 2231 AN: 86186

European-Finnish (FIN) AF: 0.0104 AC: 546 AN: 52698

Middle Eastern (MID) AF: 0.125 AC: 722 AN: 5768

European-Non Finnish (NFE) AF: 0.00966 AC: 10741 AN: 1111748

Other (OTH) AF: 0.0386 AC: 2329 AN: 60374

GnomAD4 genome AF: 0.105 AC: 15978 AN: 152142 Hom.: 2279 Cov.: 31 AF XY: 0.103 AC XY: 7659 AN XY: 74394

African (AFR) AF: 0.326 AC: 13499 AN: 41454

American (AMR) AF: 0.0670 AC: 1024 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4816

European-Finnish (FIN) AF: 0.00783 AC: 83 AN: 10606

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 888 AN: 68016

Other (OTH) AF: 0.0877 AC: 185 AN: 2110

Alfa AF: 0.0293 Hom.: 931

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
PhyloP100		0.66
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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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