rs2232592

Variant names:

• chr20-38355449-G-A
• rs2232592
• NM_004139.5:c.588+40G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-38355449-G-A
• chr20-38355449-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004139.5(LBP):​c.588+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,577,466 control chromosomes in the GnomAD database, including 604 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 0.020 (103 hom., cov: 31)
  • Exomes 𝑓: 0.0081 (501 hom.)
• Consequence: LBP NM_004139.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LBP	NM_004139.5	c.588+40G>A		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.588+40G>A		intron_variant	Intron 5 of 14	1	NM_004139.5	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 3017 AN: 152176 Hom.: 98 Cov.: 31

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0255 AC: 6342 AN: 248636 AF XY: 0.0214

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.0634

Gnomad ASJ exome AF: 0.00271

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.000734

Gnomad OTH exome AF: 0.0178

GnomAD4 exome AF: 0.00811 AC: 11565 AN: 1425172 Hom.: 501 Cov.: 26 AF XY: 0.00756 AC XY: 5376 AN XY: 711086

African (AFR) AF: 0.0365 AC: 1198 AN: 32792

American (AMR) AF: 0.0601 AC: 2681 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.00309 AC: 80 AN: 25892

East Asian (EAS) AF: 0.128 AC: 5039 AN: 39510

South Asian (SAS) AF: 0.00400 AC: 342 AN: 85452

European-Finnish (FIN) AF: 0.0178 AC: 936 AN: 52602

Middle Eastern (MID) AF: 0.00264 AC: 15 AN: 5686

European-Non Finnish (NFE) AF: 0.000289 AC: 312 AN: 1079510

Other (OTH) AF: 0.0163 AC: 962 AN: 59128

GnomAD4 genome AF: 0.0200 AC: 3046 AN: 152294 Hom.: 103 Cov.: 31 AF XY: 0.0215 AC XY: 1601 AN XY: 74460

African (AFR) AF: 0.0347 AC: 1444 AN: 41572

American (AMR) AF: 0.0327 AC: 501 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3468

East Asian (EAS) AF: 0.140 AC: 723 AN: 5172

South Asian (SAS) AF: 0.0110 AC: 53 AN: 4822

European-Finnish (FIN) AF: 0.0199 AC: 211 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68028

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.00509 Hom.: 3

Bravo AF: 0.0244

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.54
DANN	Benign	0.72
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2232592; hg19: chr20-36983849; COSMIC: COSV54140508;