NM_004139.5:c.276G>A

Variant names:

• chr20-38350847-G-A
• rs5744203
• NM_004139.5:c.276G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004139.5(LBP):​c.276G>A​(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00139 in 1,613,664 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (3 hom.)
• Consequence: LBP NM_004139.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.44
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 20-38350847-G-A is Benign according to our data. Variant chr20-38350847-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 735262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.276G>A	p.Ala92Ala	synonymous	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.276G>A	p.Ala92Ala	synonymous	Exon 3 of 15	ENSP00000217407.2	P18428
	LBP	ENST00000901257.1		c.333G>A	p.Ala111Ala	synonymous	Exon 3 of 15	ENSP00000571316.1
	LBP	ENST00000901253.1		c.276G>A	p.Ala92Ala	synonymous	Exon 3 of 15	ENSP00000571312.1

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 156 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00107 AC: 268 AN: 251022 AF XY: 0.00114

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.000278

Gnomad NFE exome AF: 0.00180

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00142 AC: 2081 AN: 1461342 Hom.: 3 Cov.: 30 AF XY: 0.00137 AC XY: 998 AN XY: 726920

African (AFR) AF: 0.000418 AC: 14 AN: 33462

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39690

South Asian (SAS) AF: 0.000522 AC: 45 AN: 86242

European-Finnish (FIN) AF: 0.000300 AC: 16 AN: 53246

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.00169 AC: 1876 AN: 1111704

Other (OTH) AF: 0.00139 AC: 84 AN: 60382

GnomAD4 genome AF: 0.00102 AC: 156 AN: 152322 Hom.: 0 Cov.: 33 AF XY: 0.00103 AC XY: 77 AN XY: 74492

African (AFR) AF: 0.000289 AC: 12 AN: 41580

American (AMR) AF: 0.000588 AC: 9 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00138 Hom.: 0

Bravo AF: 0.00107

EpiCase AF: 0.00245

EpiControl AF: 0.00296

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.26
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism

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: rs5744203; hg19: chr20-36979250;