Variant 20-38311882-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001725.3(BPI):c.545T>C(p.Ile182Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BPI
NM_001725.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BPI	NM_001725.3 linkuse as main transcript	c.545T>C	p.Ile182Thr	missense_variant	5/15	ENST00000642449.2
BPI	XM_047440393.1 linkuse as main transcript	c.557T>C	p.Ile186Thr	missense_variant	5/13
BPI	XM_047440394.1 linkuse as main transcript	c.557T>C	p.Ile186Thr	missense_variant	5/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BPI	ENST00000642449.2 linkuse as main transcript	c.545T>C	p.Ile182Thr	missense_variant	5/15		NM_001725.3	P1
BPI	ENST00000262865.9 linkuse as main transcript	c.557T>C	p.Ile186Thr	missense_variant	5/15	1
	ENST00000437016.1 linkuse as main transcript	n.183+14472A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251446

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.557T>C (p.I186T) alteration is located in exon 5 (coding exon 5) of the BPI gene. This alteration results from a T to C substitution at nucleotide position 557, causing the isoleucine (I) at amino acid position 186 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Benign

0.18

Eigen_PC

Benign

0.046

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.77

M_CAP

Benign

0.0071

MetaRNN

Uncertain

0.68

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.58

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.25

Sift

Benign

0.032

Sift4G

Uncertain

0.055

Polyphen

0.98

Vest4

0.48

MutPred

0.76

Loss of stability (P = 0.0381);

MVP

0.36

MPC

0.31

ClinPred

0.97

GERP RS

3.5

Varity_R

0.81

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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