20-38360615-T-C

Variant names:

• chr20-38360615-T-C
• rs1780623
• NM_004139.5:c.589-89T>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.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
• Publications: 9 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 (Cadd=0.103).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 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.589-89T>C		intron	N/A	NP_004130.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.589-89T>C		intron	N/A	ENSP00000217407.2	P18428
	LBP	ENST00000901257.1		c.646-89T>C		intron	N/A	ENSP00000571316.1
	LBP	ENST00000901253.1		c.589-89T>C		intron	N/A	ENSP00000571312.1

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

African (AFR) AF: 0.814 AC: 14237 AN: 17496

American (AMR) AF: 0.553 AC: 20595 AN: 37260

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 10492 AN: 18478

East Asian (EAS) AF: 0.285 AC: 9920 AN: 34846

South Asian (SAS) AF: 0.626 AC: 38258 AN: 61080

European-Finnish (FIN) AF: 0.644 AC: 32435 AN: 50330

Middle Eastern (MID) AF: 0.624 AC: 2464 AN: 3948

European-Non Finnish (NFE) AF: 0.645 AC: 257525 AN: 399322

Other (OTH) AF: 0.618 AC: 20203 AN: 32712

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

African (AFR) AF: 0.809 AC: 33588 AN: 41502

American (AMR) AF: 0.596 AC: 9109 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1681 AN: 5166

South Asian (SAS) AF: 0.590 AC: 2842 AN: 4816

European-Finnish (FIN) AF: 0.644 AC: 6787 AN: 10542

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42597 AN: 67972

Other (OTH) AF: 0.630 AC: 1331 AN: 2112

Alfa AF: 0.644 Hom.: 7729

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.10
PhyloP100		-1.8

Splicing

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

Other links and lift over

dbSNP: rs1780623;