rs2232618

Variant names:

• chr20-38373117-T-C
• rs2232618
• NM_004139.5:c.1306T>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.1306T>C​(p.Phe436Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 1,612,544 control chromosomes in the GnomAD database, including 8,096 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.12 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6830 hom.)
• Consequence: LBP NM_004139.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 47 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=0.021943927).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004139.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	NM_004139.5	MANE Select	c.1306T>C	p.Phe436Leu	missense	Exon 13 of 15	NP_004130.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.1306T>C	p.Phe436Leu	missense	Exon 13 of 15	ENSP00000217407.2
	LBP	ENST00000901257.1		c.1363T>C	p.Phe455Leu	missense	Exon 13 of 15	ENSP00000571316.1
	LBP	ENST00000901253.1		c.1297T>C	p.Phe433Leu	missense	Exon 13 of 15	ENSP00000571312.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17709 AN: 152058 Hom.: 1259 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.0893

GnomAD2 exomes AF: 0.0923 AC: 23217 AN: 251434 AF XY: 0.0961

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0393

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.0471

Gnomad FIN exome AF: 0.0674

Gnomad NFE exome AF: 0.0895

Gnomad OTH exome AF: 0.0867

GnomAD4 exome AF: 0.0914 AC: 133405 AN: 1460366 Hom.: 6830 Cov.: 30 AF XY: 0.0932 AC XY: 67713 AN XY: 726556

African (AFR) AF: 0.199 AC: 6664 AN: 33432

American (AMR) AF: 0.0437 AC: 1953 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 2392 AN: 26132

East Asian (EAS) AF: 0.0364 AC: 1444 AN: 39692

South Asian (SAS) AF: 0.150 AC: 12888 AN: 86176

European-Finnish (FIN) AF: 0.0686 AC: 3664 AN: 53408

Middle Eastern (MID) AF: 0.114 AC: 655 AN: 5764

European-Non Finnish (NFE) AF: 0.0883 AC: 98085 AN: 1110706

Other (OTH) AF: 0.0938 AC: 5660 AN: 60334

GnomAD4 genome AF: 0.117 AC: 17745 AN: 152178 Hom.: 1266 Cov.: 32 AF XY: 0.116 AC XY: 8626 AN XY: 74392

African (AFR) AF: 0.201 AC: 8346 AN: 41486

American (AMR) AF: 0.0693 AC: 1060 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3466

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5180

South Asian (SAS) AF: 0.149 AC: 716 AN: 4814

European-Finnish (FIN) AF: 0.0715 AC: 758 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0882 AC: 5997 AN: 68012

Other (OTH) AF: 0.0917 AC: 194 AN: 2116

Alfa AF: 0.0980 Hom.: 2948

Bravo AF: 0.117

TwinsUK AF: 0.0758 AC: 281

ALSPAC AF: 0.0843 AC: 325

ESP6500AA AF: 0.191 AC: 843

ESP6500EA AF: 0.0900 AC: 774

ExAC AF: 0.0964 AC: 11709

Asia WGS AF: 0.106 AC: 366 AN: 3478

EpiCase AF: 0.0964

EpiControl AF: 0.0906

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.23
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-0.51
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.015
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0090
MutPred		0.26		Loss of stability (P = 0.07)
MPC		0.11
ClinPred		0.0012	T
GERP RS		-1.0
Varity_R		0.052
gMVP		0.27
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2232618; hg19: chr20-37001761; COSMIC: COSV54143579;