rs1739654

Variant names:

• chr20-38349567-A-G
• rs1739654
• NM_004139.5:c.144A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004139.5(LBP):​c.144A>G​(p.Leu48Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 1,608,104 control chromosomes in the GnomAD database, including 710,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (61637 hom., cov: 31)
  • Exomes 𝑓: 0.94 (648789 hom.)
• Consequence: LBP NM_004139.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.787
• Publications: 16 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 20-38349567-A-G is Benign according to our data. Variant chr20-38349567-A-G is described in ClinVar as Benign. ClinVar VariationId is 769090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.787 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.144A>G	p.Leu48Leu	synonymous	Exon 2 of 15	NP_004130.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.144A>G	p.Leu48Leu	synonymous	Exon 2 of 15	ENSP00000217407.2	P18428
	LBP	ENST00000901257.1		c.201A>G	p.Leu67Leu	synonymous	Exon 2 of 15	ENSP00000571316.1
	LBP	ENST00000901253.1		c.144A>G	p.Leu48Leu	synonymous	Exon 2 of 15	ENSP00000571312.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136455 AN: 152028 Hom.: 61600 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.893

GnomAD4 exome AF: 0.943 AC: 1373147 AN: 1455958 Hom.: 648789 Cov.: 50 AF XY: 0.941 AC XY: 681195 AN XY: 723528

African (AFR) AF: 0.793 AC: 26478 AN: 33402

American (AMR) AF: 0.903 AC: 39653 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 23279 AN: 25972

East Asian (EAS) AF: 0.849 AC: 33571 AN: 39540

South Asian (SAS) AF: 0.877 AC: 74423 AN: 84894

European-Finnish (FIN) AF: 0.941 AC: 49514 AN: 52636

Middle Eastern (MID) AF: 0.827 AC: 4763 AN: 5758

European-Non Finnish (NFE) AF: 0.961 AC: 1066228 AN: 1109658

Other (OTH) AF: 0.918 AC: 55238 AN: 60174

GnomAD4 genome AF: 0.897 AC: 136545 AN: 152146 Hom.: 61637 Cov.: 31 AF XY: 0.896 AC XY: 66691 AN XY: 74400

African (AFR) AF: 0.801 AC: 33231 AN: 41488

American (AMR) AF: 0.902 AC: 13780 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4312 AN: 5144

South Asian (SAS) AF: 0.870 AC: 4197 AN: 4822

European-Finnish (FIN) AF: 0.939 AC: 9954 AN: 10604

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64982 AN: 68024

Other (OTH) AF: 0.893 AC: 1885 AN: 2112

Alfa AF: 0.933 Hom.: 104106

Bravo AF: 0.891

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.4
PhyloP100		0.79

Splicing

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

Other links and lift over

dbSNP: rs1739654; hg19: chr20-36977970;