rs1739654

Positions:

• chr20-38349567-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004139.5(LBP):​c.144A>G​(p.Leu48=) 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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LBP	NM_004139.5	c.144A>G	p.Leu48=	synonymous_variant	2/15	ENST00000217407.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LBP	ENST00000217407.3	c.144A>G	p.Leu48=	synonymous_variant	2/15	1	NM_004139.5	P1

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

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.903

Gnomad4 ASJ exome AF: 0.896

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.941

Gnomad4 NFE exome AF: 0.961

Gnomad4 OTH exome AF: 0.918

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

Gnomad4 AFR AF: 0.801

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.894

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.939

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.893

Alfa AF: 0.938 Hom.: 86286

Bravo AF: 0.891

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1739654; hg19: chr20-36977970;