dbSNP rs4358188: BPI:p.Glu212Lys (chr20-38318446-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001725.3(BPI):c.634G>A(p.Glu212Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 1,612,388 control chromosomes in the GnomAD database, including 185,568 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 17923 hom., cov: 32)

Exomes 𝑓: 0.48 ( 167645 hom. )

Consequence

BPI
NM_001725.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.10

Variant links:

Genes affected

BPI (HGNC:1095): (bactericidal permeability increasing protein) This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms. [provided by RefSeq, Nov 2014]

BPI links:

ENSG00000206249 (HGNC:):

ENSG00000206249 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4498378E-5).

BP6

Variant 20-38318446-G-A is Benign according to our data. Variant chr20-38318446-G-A is described in ClinVar as [Benign]. Clinvar id is 402434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPI	NM_001725.3 link	c.634G>A	p.Glu212Lys	missense_variant	Exon 6 of 15	ENST00000642449.2	NP_001716.3	P17213

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPI	ENST00000642449.2 link	c.634G>A	p.Glu212Lys	missense_variant	Exon 6 of 15		NM_001725.3	ENSP00000494528.2		A0A2R8YDF1

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73171

AN:

151872

Hom.:

17936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.503

Gnomad AMI

AF:

0.597

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.485

Gnomad OTH

AF:

0.439

GnomAD3 exomes

AF:

0.457

AC:

114929

AN:

251394

Hom.:

27241

AF XY:

0.464

AC XY:

62974

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.504

Gnomad AMR exome

AF:

0.385

Gnomad ASJ exome

AF:

0.401

Gnomad EAS exome

AF:

0.225

Gnomad SAS exome

AF:

0.497

Gnomad FIN exome

AF:

0.560

Gnomad NFE exome

AF:

0.485

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.475

AC:

694061

AN:

1460398

Hom.:

167645

Cov.:

AF XY:

0.477

AC XY:

346556

AN XY:

726588

show subpopulations

Gnomad4 AFR exome

AF:

0.507

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.504

Gnomad4 FIN exome

AF:

0.559

Gnomad4 NFE exome

AF:

0.484

Gnomad4 OTH exome

AF:

0.461

GnomAD4 genome

AF:

0.481

AC:

73167

AN:

151990

Hom.:

17923

Cov.:

AF XY:

0.482

AC XY:

35832

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.502

Gnomad4 AMR

AF:

0.444

Gnomad4 ASJ

AF:

0.406

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.485

Gnomad4 OTH

AF:

0.433

Alfa

AF:

0.471

Hom.:

36215

Bravo

AF:

0.468

TwinsUK

AF:

0.478

AC:

1774

ALSPAC

AF:

0.472

AC:

1821

ESP6500AA

AF:

0.502

AC:

2214

ESP6500EA

AF:

0.492

AC:

4228

ExAC

AF:

0.462

AC:

56132

Asia WGS

AF:

0.356

AC:

1239

AN:

3478

EpiCase

AF:

0.467

EpiControl

AF:

0.466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.041

DANN

Benign

0.68

DEOGEN2

Benign

0.0044

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0025

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.000014

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.0

N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.10

N;.

REVEL

Benign

0.20

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.071

MPC

0.054

ClinPred

0.0012

GERP RS

0.59

Varity_R

0.11

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over