dbSNP rs2232578: LBP:c.-205G>A (chr20-38346312-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004139.5(LBP):c.-205G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 575,976 control chromosomes in the GnomAD database, including 177,204 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 0.76 ( 44038 hom., cov: 32)

Exomes 𝑓: 0.79 ( 133166 hom. )

Consequence

LBP
NM_004139.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00700

Publications

15 publications found

Variant links:

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]

LBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5 link	c.-205G>A		upstream_gene_variant		ENST00000217407.3	NP_004130.2	P18428Q8TCF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3 link	c.-205G>A		upstream_gene_variant		1	NM_004139.5	ENSP00000217407.2		P18428

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115082

AN:

151944

Hom.:

44023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.933

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.835

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.807

Gnomad OTH

AF:

0.779

GnomAD4 exome

AF:

0.790

AC:

334886

AN:

423914

Hom.:

133166

Cov.:

AF XY:

0.783

AC XY:

174252

AN XY:

222596

show subpopulations

African (AFR)

AF:

0.644

AC:

7417

AN:

11510

American (AMR)

AF:

0.836

AC:

13877

AN:

16592

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

9266

AN:

12068

East Asian (EAS)

AF:

0.789

AC:

21230

AN:

26892

South Asian (SAS)

AF:

0.671

AC:

30215

AN:

45004

European-Finnish (FIN)

AF:

0.837

AC:

21644

AN:

25866

Middle Eastern (MID)

AF:

0.697

AC:

1187

AN:

1702

European-Non Finnish (NFE)

AF:

0.812

AC:

211662

AN:

260818

Other (OTH)

AF:

0.784

AC:

18388

AN:

23462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

3240

6480

9719

12959

16199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1382

2764

4146

5528

6910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.757

AC:

115141

AN:

152062

Hom.:

44038

Cov.:

AF XY:

0.757

AC XY:

56265

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.640

AC:

26513

AN:

41426

American (AMR)

AF:

0.818

AC:

12517

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.756

AC:

2622

AN:

3466

East Asian (EAS)

AF:

0.756

AC:

3889

AN:

5144

South Asian (SAS)

AF:

0.667

AC:

3215

AN:

4818

European-Finnish (FIN)

AF:

0.835

AC:

8852

AN:

10598

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.807

AC:

54853

AN:

67996

Other (OTH)

AF:

0.777

AC:

1642

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1410

2820

4230

5640

7050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.792

Hom.:

88711

Bravo

AF:

0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.2

(source)

PhyloP100

0.0070

PromoterAI

-0.040

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over