chr17-48596658-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_018952.5(HOXB6):c.430C>G(p.Pro144Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
HOXB6
NM_018952.5 missense
NM_018952.5 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.20
Publications
0 publications found
Genes affected
HOXB6 (HGNC:5117): (homeobox B6) This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development, including that of lung and skin, and has been localized to both the nucleus and cytoplasm. Altered expression of this gene or a change in the subcellular localization of its protein is associated with some cases of acute myeloid leukemia and colorectal cancer. [provided by RefSeq, Jul 2008]
HOXB-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)
HOXB3 (HGNC:5114): (homeobox B3) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.16202354).
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152210
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 250462 AF XY: 0.00000738 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
250462
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460886Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 726806 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1460886
Hom.:
Cov.:
33
AF XY:
AC XY:
5
AN XY:
726806
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
5
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
52434
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1112000
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000197 AC: 3AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152210
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74348
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41454
American (AMR)
AF:
AC:
2
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5188
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68036
Other (OTH)
AF:
AC:
1
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Aug 01, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.430C>G (p.P144A) alteration is located in exon 4 (coding exon 2) of the HOXB6 gene. This alteration results from a C to G substitution at nucleotide position 430, causing the proline (P) at amino acid position 144 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Gain of methylation at R147 (P = 0.0639);Gain of methylation at R147 (P = 0.0639);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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