15-60005308-C-G

Variant summary

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

The NM_012182.3(FOXB1):​c.345C>G​(p.Asp115Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 0.0 ( 0 hom., cov: 32)
Failed GnomAD Quality Control

Consequence

FOXB1
NM_012182.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103
Variant links:
Genes affected
FOXB1 (HGNC:3799): (forkhead box B1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including mammary gland development; nervous system development; and visual learning. Predicted to act upstream of or within spinal cord development; thalamus development; and urogenital system development. Predicted to be located in nucleus. Predicted to be part of chromatin. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07399216).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXB1NM_012182.3 linkc.345C>G p.Asp115Glu missense_variant Exon 2 of 2 ENST00000396057.6 NP_036314.2 Q99853

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXB1ENST00000396057.6 linkc.345C>G p.Asp115Glu missense_variant Exon 2 of 2 1 NM_012182.3 ENSP00000379369.4 Q99853
FOXB1ENST00000560857.1 linkn.410+665C>G intron_variant Intron 1 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152218
Hom.:
0
Cov.:
32
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74360
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:
0.00
Gnomad4 OTH
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 30, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.345C>G (p.D115E) alteration is located in exon 2 (coding exon 1) of the FOXB1 gene. This alteration results from a C to G substitution at nucleotide position 345, causing the aspartic acid (D) at amino acid position 115 to be replaced by a glutamic acid (E). 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
-0.034
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
16
DANN
Benign
0.84
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.87
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.074
T
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
0.53
N
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.44
N
REVEL
Uncertain
0.33
Sift
Benign
0.72
T
Sift4G
Benign
0.48
T
Polyphen
0.0010
B
Vest4
0.029
MutPred
0.20
Loss of MoRF binding (P = 0.1216);
MVP
0.51
MPC
0.79
ClinPred
0.11
T
GERP RS
1.8
Varity_R
0.061
gMVP
0.65

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-60297507; API