rs4358188

Variant names:

• chr20-38318446-G-A
• rs4358188
• NM_001725.3:c.634G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-38318446-G-A
• chr20-38318446-G-C
• chr20-38318446-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E212Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.48 (17923 hom., cov: 32)
  • Exomes 𝑓: 0.48 (167645 hom.)
• Consequence: BPI NM_001725.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10
• Publications: 59 publications found

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]

ENSG00000206249 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001725.3. 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
	BPI	NM_001725.3	MANE Select	c.634G>A	p.Glu212Lys	missense	Exon 6 of 15	NP_001716.3	A0A2R8YDF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPI	ENST00000642449.2	MANE Select	c.634G>A	p.Glu212Lys	missense	Exon 6 of 15	ENSP00000494528.2	A0A2R8YDF1
	BPI	ENST00000262865.10	TSL:1	c.634G>A	p.Glu212Lys	missense	Exon 9 of 16	ENSP00000262865.5	P17213
	BPI	ENST00000716802.1		c.634G>A	p.Glu212Lys	missense	Exon 8 of 17	ENSP00000520600.1	A0A2R8YDF1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73171 AN: 151872 Hom.: 17936 Cov.: 32

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

GnomAD2 exomes AF: 0.457 AC: 114929 AN: 251394 AF XY: 0.464

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 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.: 53 AF XY: 0.477 AC XY: 346556 AN XY: 726588

African (AFR) AF: 0.507 AC: 16964 AN: 33440

American (AMR) AF: 0.391 AC: 17498 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10395 AN: 26124

East Asian (EAS) AF: 0.207 AC: 8231 AN: 39694

South Asian (SAS) AF: 0.504 AC: 43441 AN: 86212

European-Finnish (FIN) AF: 0.559 AC: 29850 AN: 53410

Middle Eastern (MID) AF: 0.442 AC: 2548 AN: 5768

European-Non Finnish (NFE) AF: 0.484 AC: 537287 AN: 1110680

Other (OTH) AF: 0.461 AC: 27847 AN: 60346

GnomAD4 genome AF: 0.481 AC: 73167 AN: 151990 Hom.: 17923 Cov.: 32 AF XY: 0.482 AC XY: 35832 AN XY: 74302

African (AFR) AF: 0.502 AC: 20822 AN: 41448

American (AMR) AF: 0.444 AC: 6777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1410 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1134 AN: 5164

South Asian (SAS) AF: 0.513 AC: 2472 AN: 4818

European-Finnish (FIN) AF: 0.570 AC: 6013 AN: 10552

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32960 AN: 67952

Other (OTH) AF: 0.433 AC: 915 AN: 2112

Alfa AF: 0.473 Hom.: 49407

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.67	T
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	N
LIST_S2	Benign	0.37	T
MetaRNN	Benign	0.000015	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-2.0	N
PhyloP100		-1.1
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.071
MPC		0.054
ClinPred		0.0012	T
GERP RS		0.59
Varity_R		0.11
gMVP		0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs4358188; hg19: chr20-36946848; COSMIC: COSV53404412; COSMIC: COSV53404412;