20-38360727-A-G

Variant names:

• chr20-38360727-A-G
• rs2232596
• NM_004139.5:c.612A>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.612A>G​(p.Ser204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 1,611,950 control chromosomes in the GnomAD database, including 177,042 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15754 hom., cov: 31)
  • Exomes 𝑓: 0.46 (161288 hom.)
• Consequence: LBP NM_004139.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.648
• Publications: 32 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=-0.91).
• BP6: Variant 20-38360727-A-G is Benign according to our data. Variant chr20-38360727-A-G is described in ClinVar as Benign. ClinVar VariationId is 769469.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.648 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	NM_004139.5	MANE Select	c.612A>G	p.Ser204Ser	synonymous	Exon 6 of 15	NP_004130.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LBP	ENST00000217407.3	TSL:1 MANE Select	c.612A>G	p.Ser204Ser	synonymous	Exon 6 of 15	ENSP00000217407.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68012 AN: 151878 Hom.: 15749 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.464 AC: 676975 AN: 1459952 Hom.: 161288 Cov.: 32 AF XY: 0.462 AC XY: 335292 AN XY: 726406

African (AFR) AF: 0.387 AC: 12930 AN: 33424

American (AMR) AF: 0.403 AC: 18015 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 12378 AN: 26108

East Asian (EAS) AF: 0.109 AC: 4339 AN: 39686

South Asian (SAS) AF: 0.382 AC: 32940 AN: 86202

European-Finnish (FIN) AF: 0.548 AC: 29201 AN: 53332

Middle Eastern (MID) AF: 0.401 AC: 2313 AN: 5764

European-Non Finnish (NFE) AF: 0.485 AC: 538063 AN: 1110430

Other (OTH) AF: 0.444 AC: 26796 AN: 60306

GnomAD4 genome AF: 0.448 AC: 68048 AN: 151998 Hom.: 15754 Cov.: 31 AF XY: 0.446 AC XY: 33127 AN XY: 74268

African (AFR) AF: 0.390 AC: 16149 AN: 41452

American (AMR) AF: 0.452 AC: 6892 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.129 AC: 669 AN: 5174

South Asian (SAS) AF: 0.355 AC: 1713 AN: 4826

European-Finnish (FIN) AF: 0.550 AC: 5795 AN: 10528

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33563 AN: 67978

Other (OTH) AF: 0.434 AC: 915 AN: 2110

Alfa AF: 0.464 Hom.: 31619

Bravo AF: 0.434

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.047
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs2232596; hg19: chr20-36989381;