Variant chr20-33288875-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033197.3(BPIFB1):c.250A>G(p.Ile84Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,612,544 control chromosomes in the GnomAD database, including 65,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 9037 hom., cov: 32)

Exomes 𝑓: 0.27 ( 56660 hom. )

Consequence

BPIFB1
NM_033197.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.666

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.6303868E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BPIFB1	NM_033197.3 linkuse as main transcript	c.250A>G	p.Ile84Val	missense_variant	3/16	ENST00000253354.2	NP_149974.2	Q8TDL5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2 linkuse as main transcript	c.250A>G	p.Ile84Val	missense_variant	3/16	1	NM_033197.3	ENSP00000253354.1		Q8TDL5-1
BPIFB1	ENST00000423645.5 linkuse as main transcript	c.250A>G	p.Ile84Val	missense_variant	3/5	3		ENSP00000390471.1		A2A2R0

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50592

AN:

152004

Hom.:

9019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.301

AC:

74153

AN:

246746

Hom.:

12026

AF XY:

0.289

AC XY:

38618

AN XY:

133790

show subpopulations

Gnomad AFR exome

AF:

0.465

Gnomad AMR exome

AF:

0.435

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.232

Gnomad SAS exome

AF:

0.195

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.274

AC:

399977

AN:

1460422

Hom.:

56660

Cov.:

AF XY:

0.271

AC XY:

196816

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.467

Gnomad4 AMR exome

AF:

0.427

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.246

Gnomad4 SAS exome

AF:

0.191

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.333

AC:

50666

AN:

152122

Hom.:

9037

Cov.:

AF XY:

0.330

AC XY:

24555

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.458

Gnomad4 AMR

AF:

0.377

Gnomad4 ASJ

AF:

0.360

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.197

Gnomad4 FIN

AF:

0.266

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.284

Hom.:

14855

Bravo

AF:

0.352

TwinsUK

AF:

0.264

AC:

978

ALSPAC

AF:

0.259

AC:

998

ESP6500AA

AF:

0.446

AC:

1964

ESP6500EA

AF:

0.288

AC:

2478

ExAC

AF:

0.294

AC:

35680

Asia WGS

AF:

0.248

AC:

864

AN:

3478

EpiCase

AF:

0.283

EpiControl

AF:

0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.8

DANN

Benign

0.34

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.00046

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.036

Sift

Benign

0.16

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.016

.;B

Vest4

0.040

MPC

0.18

ClinPred

0.0035

GERP RS

1.8

Varity_R

0.036

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over