chr7-151148980-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001098834.3(GBX1):​c.701C>T​(p.Pro234Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,613,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

GBX1
NM_001098834.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.135
Variant links:
Genes affected
GBX1 (HGNC:4185): (gastrulation brain homeobox 1) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of nervous system development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within adult walking behavior; neuron differentiation; and proprioception. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.050406545).
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GBX1NM_001098834.3 linkuse as main transcriptc.701C>T p.Pro234Leu missense_variant 2/2 ENST00000297537.5 NP_001092304.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GBX1ENST00000297537.5 linkuse as main transcriptc.701C>T p.Pro234Leu missense_variant 2/21 NM_001098834.3 ENSP00000297537 P1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152036
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000725
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000561
AC:
14
AN:
249466
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000501
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000105
AC:
154
AN:
1461812
Hom.:
0
Cov.:
32
AF XY:
0.000117
AC XY:
85
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00141
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000773
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0000723
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000330
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.000262
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000414
AC:
5
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsMar 29, 2022The c.701C>T (p.P234L) alteration is located in exon 2 (coding exon 2) of the GBX1 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the proline (P) at amino acid position 234 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
0.10
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.050
T
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
0.99
D
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-2.5
D
REVEL
Benign
0.28
Sift
Benign
0.035
D
Sift4G
Benign
0.091
T
Polyphen
0.0030
B
Vest4
0.085
MVP
0.83
MPC
0.78
ClinPred
0.051
T
GERP RS
3.9
Varity_R
0.11
gMVP
0.22

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: rs375529208; hg19: chr7-150846067; COSMIC: COSV52546864; COSMIC: COSV52546864; API