dbSNP rs2093066: BPIFB3:p.Thr286Met (chr20-33064790-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.857C>T(p.Thr286Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,842 control chromosomes in the GnomAD database, including 16,593 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 0.14 ( 1785 hom., cov: 31)

Exomes 𝑓: 0.14 ( 14808 hom. )

Consequence

BPIFB3
NM_001376932.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.03

Publications

18 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=0.0036616623).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB3	NM_001376932.3 link	c.857C>T	p.Thr286Met	missense_variant	Exon 9 of 16	ENST00000375494.4	NP_001363861.2
BPIFB3	NM_182658.5 link	c.857C>T	p.Thr286Met	missense_variant	Exon 8 of 15		NP_872599.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BPIFB3	ENST00000375494.4 link	c.857C>T	p.Thr286Met	missense_variant	Exon 9 of 16	1	NM_001376932.3	ENSP00000364643.4

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21877

AN:

151992

Hom.:

1776

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0874

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0483

Gnomad SAS

AF:

0.0606

Gnomad FIN

AF:

0.0678

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.151

GnomAD2 exomes

AF:

0.113

AC:

28419

AN:

251200

AF XY:

0.112

show subpopulations

Gnomad AFR exome

AF:

0.213

Gnomad AMR exome

AF:

0.0629

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.0504

Gnomad FIN exome

AF:

0.0712

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.137

AC:

199924

AN:

1461732

Hom.:

14808

Cov.:

AF XY:

0.134

AC XY:

97675

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.221

AC:

7388

AN:

33474

American (AMR)

AF:

0.0673

AC:

3009

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4420

AN:

26134

East Asian (EAS)

AF:

0.0465

AC:

1847

AN:

39700

South Asian (SAS)

AF:

0.0739

AC:

6374

AN:

86258

European-Finnish (FIN)

AF:

0.0689

AC:

3677

AN:

53332

Middle Eastern (MID)

AF:

0.143

AC:

825

AN:

5766

European-Non Finnish (NFE)

AF:

0.148

AC:

164208

AN:

1111954

Other (OTH)

AF:

0.135

AC:

8176

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

10000

20001

30001

40002

50002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5912

11824

17736

23648

29560

<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:

0.144

AC:

21896

AN:

152110

Hom.:

1785

Cov.:

AF XY:

0.136

AC XY:

10096

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.217

AC:

9017

AN:

41470

American (AMR)

AF:

0.0873

AC:

1334

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

520

AN:

3470

East Asian (EAS)

AF:

0.0483

AC:

250

AN:

5180

South Asian (SAS)

AF:

0.0600

AC:

289

AN:

4816

European-Finnish (FIN)

AF:

0.0678

AC:

719

AN:

10604

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9330

AN:

67972

Other (OTH)

AF:

0.154

AC:

324

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

960

1920

2880

3840

4800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.141

Hom.:

7195

Bravo

AF:

0.151

TwinsUK

AF:

0.145

AC:

536

ALSPAC

AF:

0.149

AC:

574

ESP6500AA

AF:

0.204

AC:

900

ESP6500EA

AF:

0.145

AC:

1249

ExAC

AF:

0.115

AC:

13973

Asia WGS

AF:

0.0790

AC:

273

AN:

3478

EpiCase

AF:

0.145

EpiControl

AF:

0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.023

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.69

PhyloP100

2.0

PrimateAI

Benign

0.36

PROVEAN

Benign

0.010

REVEL

Benign

0.061

Sift

Benign

0.10

Sift4G

Uncertain

0.0090

Polyphen

0.0

Vest4

0.050

MPC

0.095

ClinPred

0.023

GERP RS

4.7

Varity_R

0.029

gMVP

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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