chr20-38363237-T-C

Variant names:

• chr20-38363237-T-C
• rs11536972
• NM_004139.5:c.653-738T>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.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
• Publications: 5 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=-0.9).
• 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 rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.653-738T>C		intron_variant	Intron 6 of 14	ENST00000217407.3	NP_004130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LBP	ENST00000217407.3	c.653-738T>C		intron_variant	Intron 6 of 14	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

African (AFR) AF: 0.0886 AC: 3680 AN: 41540

American (AMR) AF: 0.0479 AC: 733 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3472

East Asian (EAS) AF: 0.0865 AC: 449 AN: 5190

South Asian (SAS) AF: 0.135 AC: 652 AN: 4826

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10620

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0558 AC: 3796 AN: 68010

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0564 Hom.: 147

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11536972; hg19: chr20-36991891;