5-57246405-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022913.4(GPBP1):​c.584C>T​(p.Pro195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

GPBP1
NM_022913.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
Variant links:
Genes affected
GPBP1 (HGNC:29520): (GC-rich promoter binding protein 1) This gene was originally isolated by subtractive hybridization of cDNAs expressed in atherosclerotic plaques with a thrombus, and was found to be expressed only in vascular smooth muscle cells. However, a shorter splice variant was found to be more ubiquitously expressed. This protein is suggested to play a role in the development of atherosclerosis. Studies in mice suggest that it may also function as a GC-rich promoter-specific trans-activating transcription factor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05108741).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPBP1NM_022913.4 linkc.584C>T p.Pro195Leu missense_variant Exon 7 of 12 ENST00000506184.7 NP_075064.1 Q86WP2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPBP1ENST00000506184.7 linkc.584C>T p.Pro195Leu missense_variant Exon 7 of 12 1 NM_022913.4 ENSP00000421202.2 Q86WP2-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.000221
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000103
AC:
26
AN:
251274
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
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:
0.000132
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000138
AC:
201
AN:
1461602
Hom.:
0
Cov.:
31
AF XY:
0.000139
AC XY:
101
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000157
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000123
Hom.:
0
Bravo
AF:
0.000147
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
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
Dec 11, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.605C>T (p.P202L) alteration is located in exon 6 (coding exon 6) of the GPBP1 gene. This alteration results from a C to T substitution at nucleotide position 605, causing the proline (P) at amino acid position 202 to be replaced by a leucine (L). 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
0.074
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
15
DANN
Benign
0.60
DEOGEN2
Benign
0.051
.;.;T;.;.
Eigen
Benign
-0.67
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.75
T;T;T;T;T
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.051
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.64
.;.;N;.;.
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.5
D;D;D;D;D
REVEL
Benign
0.048
Sift
Benign
0.13
T;T;T;T;T
Sift4G
Benign
0.41
T;T;T;T;T
Polyphen
0.0
B;.;B;B;B
Vest4
0.20
MVP
0.068
MPC
0.35
ClinPred
0.057
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.074
gMVP
0.31

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

LitVar

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

Other links and lift over

dbSNP: rs201600135; hg19: chr5-56542232; API