dbSNP rs2070325: BPIFB4:p.Ile268Val (chr20-33086040-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_182519.3(BPIFB4):c.802A>G(p.Ile268Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,610,064 control chromosomes in the GnomAD database, including 123,985 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.36 ( 10889 hom., cov: 32)

Exomes 𝑓: 0.38 ( 113096 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

Publications

41 publications found

Variant links:

Genes affected

BPIFB4 (HGNC:16179): (BPI fold containing family B member 4) Predicted to enable lipid binding activity. Predicted to be located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

BPIFB4 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=1.7507998E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BPIFB4	NM_182519.3 link	c.802A>G	p.Ile268Val	missense_variant	Exon 7 of 18	ENST00000375483.4	NP_872325.2	P59827-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BPIFB4	ENST00000375483.4 link	c.802A>G	p.Ile268Val	missense_variant	Exon 7 of 18	5	NM_182519.3	ENSP00000364632.3	P59827-1
BPIFB4	ENST00000674031.1 link	c.1168A>G	p.Ile390Val	missense_variant	Exon 4 of 15			ENSP00000501266.1	A0A669KBJ0
BPIFB4	ENST00000445356.1 link	n.107-2926A>G		intron_variant	Intron 3 of 6	2		ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55233

AN:

151874

Hom.:

10895

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.778

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.414

AC:

104036

AN:

251404

AF XY:

0.414

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.440

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.800

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.390

GnomAD4 exome

AF:

0.385

AC:

560965

AN:

1458072

Hom.:

113096

Cov.:

AF XY:

0.386

AC XY:

279725

AN XY:

724562

show subpopulations

African (AFR)

AF:

0.259

AC:

8664

AN:

33402

American (AMR)

AF:

0.439

AC:

19629

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6978

AN:

26118

East Asian (EAS)

AF:

0.789

AC:

31241

AN:

39584

South Asian (SAS)

AF:

0.473

AC:

40805

AN:

86178

European-Finnish (FIN)

AF:

0.430

AC:

22967

AN:

53362

Middle Eastern (MID)

AF:

0.298

AC:

1688

AN:

5660

European-Non Finnish (NFE)

AF:

0.366

AC:

405532

AN:

1108918

Other (OTH)

AF:

0.390

AC:

23461

AN:

60174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

17520

35039

52559

70078

87598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13226

26452

39678

52904

66130

<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:

0.364

AC:

55255

AN:

151992

Hom.:

10889

Cov.:

AF XY:

0.373

AC XY:

27687

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.271

AC:

11226

AN:

41462

American (AMR)

AF:

0.401

AC:

6127

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

953

AN:

3472

East Asian (EAS)

AF:

0.778

AC:

4006

AN:

5150

South Asian (SAS)

AF:

0.494

AC:

2372

AN:

4802

European-Finnish (FIN)

AF:

0.449

AC:

4741

AN:

10556

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24722

AN:

67964

Other (OTH)

AF:

0.361

AC:

762

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1750

3500

5249

6999

8749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.364

Hom.:

46814

Bravo

AF:

0.358

TwinsUK

AF:

0.361

AC:

1338

ALSPAC

AF:

0.369

AC:

1423

ESP6500AA

AF:

0.266

AC:

1173

ESP6500EA

AF:

0.362

AC:

3112

ExAC

AF:

0.409

AC:

49689

Asia WGS

AF:

0.587

AC:

2039

AN:

3478

EpiCase

AF:

0.348

EpiControl

AF:

0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0027

Eigen

Benign

0.15

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

PhyloP100

2.8

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.86

REVEL

Benign

0.048

Sift

Uncertain

0.023

Sift4G

Benign

0.25

Polyphen

0.68

Vest4

0.19

MPC

0.11

ClinPred

0.018

GERP RS

3.9

Varity_R

0.086

gMVP

0.17

Mutation Taster

=78/22

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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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