Variant chr20-33286167-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033197.3(BPIFB1):c.94G>C(p.Gly32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

BPIFB1
NM_033197.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.655

Variant links:

Genes affected

BPIFB1 (HGNC:16108): (BPI fold containing family B member 1) The protein encoded by this gene may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. The encoded protein is secreted and is a member of the BPI/LBP/PLUNC protein superfamily. This gene is found with other members of the superfamily in a cluster on chromosome 20. [provided by RefSeq, Jul 2008]

BPIFB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22732669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB1	NM_033197.3 linkuse as main transcript	c.94G>C	p.Gly32Arg	missense_variant	2/16	ENST00000253354.2	NP_149974.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2 linkuse as main transcript	c.94G>C	p.Gly32Arg	missense_variant	2/16	1	NM_033197.3	ENSP00000253354	P1	Q8TDL5-1
BPIFB1	ENST00000423645.5 linkuse as main transcript	c.94G>C	p.Gly32Arg	missense_variant	2/5	3		ENSP00000390471

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251454

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000937

AC:

137

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000111

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

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 18, 2022

The c.94G>C (p.G32R) alteration is located in exon 2 (coding exon 1) of the BPIFB1 gene. This alteration results from a G to C substitution at nucleotide position 94, causing the glycine (G) at amino acid position 32 to be replaced by an arginine (R). 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

0.59

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-5.9

D;D

REVEL

Benign

0.087

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.99

.;D

Vest4

0.49

MVP

0.30

MPC

0.71

ClinPred

0.94

GERP RS

-1.0

Varity_R

0.14

gMVP

0.63

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