NM_004139.5:c.367T>C

Variant names:

• chr20-38350938-T-C
• rs1204159456
• NM_004139.5:c.367T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_004139.5(LBP):​c.367T>C​(p.Phe123Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LBP NM_004139.5 missense, splice_region
• Scores: Splicing: ADA: 0.00006981
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.17
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040956765).
• BP6: Variant 20-38350938-T-C is Benign according to our data. Variant chr20-38350938-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3117993.Status of the report is criteria_provided_single_submitter, 1 stars.

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.367T>C	p.Phe123Leu	missense splice_region	Exon 3 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.367T>C	p.Phe123Leu	missense splice_region	Exon 3 of 15	ENSP00000217407.2	P18428
	LBP	ENST00000901257.1		c.424T>C	p.Phe142Leu	missense splice_region	Exon 3 of 15	ENSP00000571316.1
	LBP	ENST00000901253.1		c.367T>C	p.Phe123Leu	missense splice_region	Exon 3 of 15	ENSP00000571312.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250824 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460884 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726564

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111338

Other (OTH) AF: 0.00 AC: 0 AN: 60342

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.073
DANN	Benign	0.65
DEOGEN2	Benign	0.019	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.7	N
PhyloP100		-3.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	0.88	T
Polyphen		0.0	B
Vest4		0.059
MutPred		0.52		Loss of catalytic residue at F123 (P = 0.0372)
MVP		0.072
MPC		0.11
ClinPred		0.073	T
GERP RS		-4.7
Varity_R		0.082
gMVP		0.23
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.0
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: rs1204159456; hg19: chr20-36979341;