chr20-38363237-T-C

Position:

• chr20-38363237-T-C

Variant summary

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

The NM_004139.5(LBP):​c.653-738T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,278 control chromosomes in the GnomAD database, including 367 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 0.064 (367 hom., cov: 31)
• Consequence: LBP NM_004139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LBP	NM_004139.5	c.653-738T>C		intron_variant		ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.653-738T>C		intron_variant		1	NM_004139.5	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9725 AN: 152160 Hom.: 365 Cov.: 31

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0558

Gnomad OTH AF: 0.0517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0639 AC: 9733 AN: 152278 Hom.: 367 Cov.: 31 AF XY: 0.0643 AC XY: 4785 AN XY: 74464

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.0479

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.0865

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0558

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0562 Hom.: 119

Bravo AF: 0.0645

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11536972; hg19: chr20-36991891;