rs2232582

Positions:

• chr20-38350862-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004139.5(LBP):​c.291T>C​(p.Pro97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,612,716 control chromosomes in the GnomAD database, including 25,928 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.

• Frequency:
  • Genomes: 𝑓 0.21 (4292 hom., cov: 33)
  • Exomes 𝑓: 0.16 (21636 hom.)
• Consequence: LBP NM_004139.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP7: Synonymous conserved (PhyloP=-2.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBP	NM_004139.5	c.291T>C	p.Pro97=	synonymous_variant	3/15	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.291T>C	p.Pro97=	synonymous_variant	3/15	1	NM_004139.5	ENSP00000217407	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32241 AN: 152160 Hom.: 4279 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.162 AC: 40549 AN: 250874 Hom.: 4044 AF XY: 0.165 AC XY: 22416 AN XY: 135554

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.0818

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.0892

Gnomad SAS exome AF: 0.233

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.164 AC: 239943 AN: 1460438 Hom.: 21636 Cov.: 32 AF XY: 0.167 AC XY: 121171 AN XY: 726382

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.0857

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.0681

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.212 AC: 32296 AN: 152278 Hom.: 4292 Cov.: 33 AF XY: 0.210 AC XY: 15617 AN XY: 74472

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.186

Alfa AF: 0.176 Hom.: 1939

Bravo AF: 0.217

Asia WGS AF: 0.155 AC: 540 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2232582; hg19: chr20-36979265; COSMIC: COSV54143636;