20-38346312-G-A

Variant names:

• chr20-38346312-G-A
• rs2232578
• NM_004139.5:c.-205G>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.-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.806 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	NM_004139.5	MANE Select	c.-205G>A		upstream_gene	N/A	NP_004130.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.-205G>A		upstream_gene	N/A	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115082 AN: 151944 Hom.: 44023 Cov.: 32

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.: 5 AF XY: 0.783 AC XY: 174252 AN XY: 222596

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

GnomAD4 genome AF: 0.757 AC: 115141 AN: 152062 Hom.: 44038 Cov.: 32 AF XY: 0.757 AC XY: 56265 AN XY: 74340

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

Alfa AF: 0.792 Hom.: 88711

Bravo AF: 0.755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.2
PhyloP100		0.0070
PromoterAI		-0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2232578; hg19: chr20-36974715;