20-33083499-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182519.3(BPIFB4):​c.302G>T​(p.Gly101Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

BPIFB4
NM_182519.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16
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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BPIFB4NM_182519.3 linkuse as main transcriptc.302G>T p.Gly101Val missense_variant 5/18 ENST00000375483.4 NP_872325.2 P59827-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BPIFB4ENST00000375483.4 linkuse as main transcriptc.302G>T p.Gly101Val missense_variant 5/185 NM_182519.3 ENSP00000364632.3 P59827-1
BPIFB4ENST00000674031.1 linkuse as main transcriptc.668G>T p.Gly223Val missense_variant 2/15 ENSP00000501266.1 A0A669KBJ0
BPIFB4ENST00000445356.1 linkuse as main transcriptn.106+1867G>T intron_variant 2 ENSP00000388423.1 F8WEG9

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
151976
Hom.:
0
Cov.:
31
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251424
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135886
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000616
AC:
90
AN:
1461842
Hom.:
0
Cov.:
36
AF XY:
0.0000523
AC XY:
38
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
151976
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 24, 2024The c.302G>T (p.G101V) alteration is located in exon 3 (coding exon 3) of the BPIFB4 gene. This alteration results from a G to T substitution at nucleotide position 302, causing the glycine (G) at amino acid position 101 to be replaced by a valine (V). 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
0.31
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0061
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.97
L
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.21
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.64
MutPred
0.46
Gain of sheet (P = 0.0061);
MVP
0.17
MPC
0.40
ClinPred
0.44
T
GERP RS
3.3
Varity_R
0.15
gMVP
0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768535365; hg19: chr20-31671305; API