rs751264766

Variant summary

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

The NM_182519.3(BPIFB4):​c.203T>C​(p.Val68Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,216 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.823

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]

Genome browser will be placed here

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=0.10676068).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BPIFB4NM_182519.3 linkc.203T>C p.Val68Ala missense_variant Exon 5 of 18 ENST00000375483.4 NP_872325.2 P59827-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BPIFB4ENST00000375483.4 linkc.203T>C p.Val68Ala missense_variant Exon 5 of 18 5 NM_182519.3 ENSP00000364632.3 P59827-1
BPIFB4ENST00000674031.1 linkc.569T>C p.Val190Ala missense_variant Exon 2 of 15 ENSP00000501266.1 A0A669KBJ0
BPIFB4ENST00000445356.1 linkn.106+1768T>C intron_variant Intron 3 of 6 2 ENSP00000388423.1 F8WEG9

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151692
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000295
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000119
AC:
3
AN:
251262
AF XY:
0.0000147
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461524
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727090
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26106
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000180
AC:
20
AN:
1111716
Other (OTH)
AF:
0.00
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000132
AC:
2
AN:
151692
Hom.:
0
Cov.:
29
AF XY:
0.0000135
AC XY:
1
AN XY:
74072
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41248
American (AMR)
AF:
0.00
AC:
0
AN:
15224
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4802
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10562
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000295
AC:
2
AN:
67908
Other (OTH)
AF:
0.00
AC:
0
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000660
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 28, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.203T>C (p.V68A) alteration is located in exon 3 (coding exon 3) of the BPIFB4 gene. This alteration results from a T to C substitution at nucleotide position 203, causing the valine (V) at amino acid position 68 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
15
DANN
Benign
0.83
DEOGEN2
Benign
0.0065
T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.47
N
LIST_S2
Benign
0.36
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.97
L
PhyloP100
0.82
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.049
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.041
D
Polyphen
0.083
B
Vest4
0.15
MutPred
0.26
Gain of loop (P = 0.0435);
MVP
0.030
MPC
0.078
ClinPred
0.13
T
GERP RS
2.9
Varity_R
0.064
gMVP
0.19
Mutation Taster
=87/13
polymorphism

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

Other links and lift over

dbSNP: rs751264766; hg19: chr20-31671206; API