20-38310511-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001725.3(BPI):ā€‹c.395A>Cā€‹(p.Asp132Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,613,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000082 ( 1 hom. )

Consequence

BPI
NM_001725.3 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430
Variant links:
Genes affected
BPI (HGNC:1095): (bactericidal permeability increasing protein) This gene encodes a lipopolysaccharide binding protein. It is associated with human neutrophil granules and has antimicrobial activity against gram-negative organisms. [provided by RefSeq, Nov 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07172379).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BPINM_001725.3 linkuse as main transcriptc.395A>C p.Asp132Ala missense_variant 4/15 ENST00000642449.2 NP_001716.3
BPIXM_047440393.1 linkuse as main transcriptc.407A>C p.Asp136Ala missense_variant 4/13 XP_047296349.1
BPIXM_047440394.1 linkuse as main transcriptc.407A>C p.Asp136Ala missense_variant 4/12 XP_047296350.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BPIENST00000642449.2 linkuse as main transcriptc.395A>C p.Asp132Ala missense_variant 4/15 NM_001725.3 ENSP00000494528 P1
BPIENST00000262865.9 linkuse as main transcriptc.407A>C p.Asp136Ala missense_variant 4/151 ENSP00000262865
ENST00000437016.1 linkuse as main transcriptn.183+15843T>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152204
Hom.:
0
Cov.:
33
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:
0.000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000179
AC:
45
AN:
251112
Hom.:
1
AF XY:
0.000162
AC XY:
22
AN XY:
135720
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:
0.00166
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000821
AC:
120
AN:
1461268
Hom.:
1
Cov.:
30
AF XY:
0.0000922
AC XY:
67
AN XY:
726834
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:
0.00142
Gnomad4 NFE exome
AF:
0.0000333
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74354
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:
0.000941
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000432
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.000107
AC:
13

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, 2023The c.407A>C (p.D136A) alteration is located in exon 4 (coding exon 4) of the BPI gene. This alteration results from a A to C substitution at nucleotide position 407, causing the aspartic acid (D) at amino acid position 136 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
0.20
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.60
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Benign
0.078
Sift
Uncertain
0.016
D
Sift4G
Uncertain
0.017
D
Polyphen
0.88
P
Vest4
0.15
MutPred
0.66
Gain of sheet (P = 0.039);
MVP
0.34
MPC
0.25
ClinPred
0.25
T
GERP RS
3.5
Varity_R
0.42
gMVP
0.51

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

LitVar

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

Other links and lift over

dbSNP: rs764359200; hg19: chr20-36938913; API