Genetic Variant BPIFB4:p.Pro73Ala (chr20-33083414-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182519.3(BPIFB4):c.217C>G(p.Pro73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P73R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.11

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1103383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BPIFB4	NM_182519.3	MANE Select	c.217C>G	p.Pro73Ala	missense	Exon 5 of 18	NP_872325.2	P59827-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BPIFB4	ENST00000375483.4	TSL:5 MANE Select	c.217C>G	p.Pro73Ala	missense	Exon 5 of 18	ENSP00000364632.3	P59827-1
BPIFB4	ENST00000674031.1		c.583C>G	p.Pro195Ala	missense	Exon 2 of 15	ENSP00000501266.1	A0A669KBJ0
BPIFB4	ENST00000445356.1	TSL:2	n.106+1782C>G		intron	N/A	ENSP00000388423.1	F8WEG9

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251378

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461606

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111768

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000198

AC:

AN:

151820

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74122

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41294

American (AMR)

AF:

0.0000655

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.67

M_CAP

Benign

0.0043

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.90

PhyloP100

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.69

REVEL

Benign

0.049

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

0.26

Vest4

0.35

MVP

0.061

MPC

0.062

ClinPred

0.063

GERP RS

1.9

Varity_R

0.055

gMVP

0.16

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over