Genetic Variant NM_033197.3:c.250A>G (chr20-33288875-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

25 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BPIFB1	NM_033197.3 link	c.250A>G	p.Ile84Val	missense_variant	Exon 3 of 16	ENST00000253354.2	NP_149974.2	Q8TDL5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB1	ENST00000253354.2 link	c.250A>G	p.Ile84Val	missense_variant	Exon 3 of 16	1	NM_033197.3	ENSP00000253354.1		Q8TDL5-1
BPIFB1	ENST00000423645.5 link	c.250A>G	p.Ile84Val	missense_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.301

AC:

74153

AN:

246746

AF XY:

0.289

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 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

African (AFR)

AF:

0.467

AC:

15630

AN:

33470

American (AMR)

AF:

0.427

AC:

19039

AN:

44620

Ashkenazi Jewish (ASJ)

AF:

0.356

AC:

9305

AN:

26122

East Asian (EAS)

AF:

0.246

AC:

9747

AN:

39680

South Asian (SAS)

AF:

0.191

AC:

16479

AN:

86202

European-Finnish (FIN)

AF:

0.266

AC:

13985

AN:

52596

Middle Eastern (MID)

AF:

0.326

AC:

1880

AN:

5766

European-Non Finnish (NFE)

AF:

0.267

AC:

296939

AN:

1111602

Other (OTH)

AF:

0.281

AC:

16973

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

14788

29575

44363

59150

73938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.333

AC:

50666

AN:

152122

Hom.:

9037

Cov.:

AF XY:

0.330

AC XY:

24555

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.458

AC:

18989

AN:

41458

American (AMR)

AF:

0.377

AC:

5773

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

1247

AN:

3468

East Asian (EAS)

AF:

0.236

AC:

1222

AN:

5168

South Asian (SAS)

AF:

0.197

AC:

951

AN:

4830

European-Finnish (FIN)

AF:

0.266

AC:

2815

AN:

10598

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.274

AC:

18648

AN:

67986

Other (OTH)

AF:

0.318

AC:

671

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1734

3468

5203

6937

8671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.290

Hom.:

28608

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

(source)

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

PhyloP100

0.67

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_033197.3:c.250A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over