rs1780623

Variant names:

• chr20-38360615-T-C
• rs1780623
• NM_004139.5:c.589-89T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004139.5(LBP):​c.589-89T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 807,534 control chromosomes in the GnomAD database, including 163,009 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 0.66 (34232 hom., cov: 31)
  • Exomes 𝑓: 0.62 (128777 hom.)
• Consequence: LBP NM_004139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.103).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.589-89T>C		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.589-89T>C		intron_variant	Intron 5 of 14	1	NM_004139.5	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100552 AN: 151944 Hom.: 34181 Cov.: 31

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.620 AC: 406129 AN: 655472 Hom.: 128777 AF XY: 0.620 AC XY: 216599 AN XY: 349268

Gnomad4 AFR exome AF: 0.814

Gnomad4 AMR exome AF: 0.553

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.626

Gnomad4 FIN exome AF: 0.644

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.618

GnomAD4 genome AF: 0.662 AC: 100665 AN: 152062 Hom.: 34232 Cov.: 31 AF XY: 0.659 AC XY: 48981 AN XY: 74342

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.630

Alfa AF: 0.641 Hom.: 7498

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.10

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1780623; hg19: -;