chr20-38349233-G-A

Variant names:

• chr20-38349233-G-A
• rs11536940
• NM_004139.5:c.125-315G>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.125-315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 152,300 control chromosomes in the GnomAD database, including 276 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 0.044 (276 hom., cov: 32)
• Consequence: LBP NM_004139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.125-315G>A		intron_variant	Intron 1 of 14	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.125-315G>A		intron_variant	Intron 1 of 14	1	NM_004139.5	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6639 AN: 152182 Hom.: 276 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.00810

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0159

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0436 AC: 6640 AN: 152300 Hom.: 276 Cov.: 32 AF XY: 0.0428 AC XY: 3187 AN XY: 74490

African (AFR) AF: 0.108 AC: 4504 AN: 41554

American (AMR) AF: 0.0358 AC: 548 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0311 AC: 150 AN: 4822

European-Finnish (FIN) AF: 0.00810 AC: 86 AN: 10622

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0158 AC: 1078 AN: 68022

Other (OTH) AF: 0.0497 AC: 105 AN: 2112

Alfa AF: 0.0215 Hom.: 130

Bravo AF: 0.0472

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.60
PhyloP100		-1.1
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: rs11536940; hg19: chr20-36977636;