dbSNP rs378098: BPIFB3:p.Pro445Ser (chr20-33072737-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001376932.3(BPIFB3):c.1333C>T(p.Pro445Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,611,942 control chromosomes in the GnomAD database, including 17,812 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2273 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15539 hom. )

Consequence

BPIFB3
NM_001376932.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.31

Publications

20 publications found

Variant links:

Genes affected

BPIFB3 (HGNC:16178): (BPI fold containing family B member 3) Predicted to enable lipid binding activity. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022091866).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB3	NM_001376932.3 link	c.1333C>T	p.Pro445Ser	missense_variant	Exon 15 of 16	ENST00000375494.4	NP_001363861.2
BPIFB3	NM_182658.5 link	c.1333C>T	p.Pro445Ser	missense_variant	Exon 14 of 15		NP_872599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB3	ENST00000375494.4 link	c.1333C>T	p.Pro445Ser	missense_variant	Exon 15 of 16	1	NM_001376932.3	ENSP00000364643.4

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24100

AN:

151994

Hom.:

2264

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0584

Gnomad AMR

AF:

0.0954

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0485

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0697

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.169

GnomAD2 exomes

AF:

0.118

AC:

29738

AN:

251438

AF XY:

0.116

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.0673

Gnomad ASJ exome

AF:

0.169

Gnomad EAS exome

AF:

0.0505

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.139

AC:

203410

AN:

1459830

Hom.:

15539

Cov.:

AF XY:

0.137

AC XY:

99405

AN XY:

726420

show subpopulations

African (AFR)

AF:

0.268

AC:

8951

AN:

33426

American (AMR)

AF:

0.0719

AC:

3214

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4424

AN:

26124

East Asian (EAS)

AF:

0.0464

AC:

1842

AN:

39684

South Asian (SAS)

AF:

0.0754

AC:

6503

AN:

86218

European-Finnish (FIN)

AF:

0.0716

AC:

3826

AN:

53418

Middle Eastern (MID)

AF:

0.142

AC:

820

AN:

5768

European-Non Finnish (NFE)

AF:

0.149

AC:

165428

AN:

1110146

Other (OTH)

AF:

0.139

AC:

8402

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

8542

17085

25627

34170

42712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5954

11908

17862

23816

29770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.159

AC:

24117

AN:

152112

Hom.:

2273

Cov.:

AF XY:

0.150

AC XY:

11159

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.263

AC:

10891

AN:

41454

American (AMR)

AF:

0.0953

AC:

1457

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

522

AN:

3472

East Asian (EAS)

AF:

0.0484

AC:

251

AN:

5186

South Asian (SAS)

AF:

0.0620

AC:

298

AN:

4810

European-Finnish (FIN)

AF:

0.0697

AC:

738

AN:

10592

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9489

AN:

67990

Other (OTH)

AF:

0.171

AC:

362

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1011

2023

3034

4046

5057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.149

Hom.:

6174

Bravo

AF:

0.168

TwinsUK

AF:

0.147

AC:

546

ALSPAC

AF:

0.152

AC:

585

ESP6500AA

AF:

0.243

AC:

1070

ESP6500EA

AF:

0.147

AC:

1261

ExAC

AF:

0.121

AC:

14686

Asia WGS

AF:

0.0770

AC:

267

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

3.3

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-5.7

REVEL

Benign

0.17

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.26

MPC

0.49

ClinPred

0.017

GERP RS

4.6

Varity_R

0.79

gMVP

0.56

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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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