20-38360442-G-A

Variant names:

• chr20-38360442-G-A
• rs12624843
• NM_004139.5:c.589-262G>A

Variant summary

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

The NM_004139.5(LBP):​c.589-262G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,004 control chromosomes in the GnomAD database, including 9,758 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 0.34 (9758 hom., cov: 31)
• Consequence: LBP NM_004139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.955
• Publications: 10 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 (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.589-262G>A		intron_variant	Intron 5 of 14	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.589-262G>A		intron_variant	Intron 5 of 14	1	NM_004139.5	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51876 AN: 151886 Hom.: 9764 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.369

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51882 AN: 152004 Hom.: 9758 Cov.: 31 AF XY: 0.345 AC XY: 25620 AN XY: 74280

African (AFR) AF: 0.189 AC: 7852 AN: 41464

American (AMR) AF: 0.430 AC: 6576 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1528 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3493 AN: 5160

South Asian (SAS) AF: 0.410 AC: 1974 AN: 4820

European-Finnish (FIN) AF: 0.360 AC: 3804 AN: 10554

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25468 AN: 67946

Other (OTH) AF: 0.370 AC: 779 AN: 2108

Alfa AF: 0.375 Hom.: 47227

Bravo AF: 0.344

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.38
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12624843; hg19: chr20-36989096;