rs553693117

Variant summary

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

The NM_024016.4(HOXB8):​c.628T>C​(p.Phe210Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F210I) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

HOXB8
NM_024016.4 missense

Scores

2
3
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.68
Variant links:
Genes affected
HOXB8 (HGNC:5119): (homeobox B8) 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 colorectal cancer. Mice that have had the murine ortholog of this gene knocked out exhibit an excessive pathologic grooming behavior. This behavior is similar to the behavior of humans suffering from the obsessive-compulsive spectrum disorder trichotillomania. [provided by RefSeq, Jul 2008]
HOXB7 (HGNC:5118): (homeobox B7) 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 nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of melanoma and ovarian carcinoma. [provided by RefSeq, Jul 2008]

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=0.14467666).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB8NM_024016.4 linkc.628T>C p.Phe210Leu missense_variant Exon 2 of 2 ENST00000239144.5 NP_076921.1 P17481Q8N8T3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXB8ENST00000239144.5 linkc.628T>C p.Phe210Leu missense_variant Exon 2 of 2 2 NM_024016.4 ENSP00000239144.4 P17481
HOXB8ENST00000576562.1 linkc.625T>C p.Phe209Leu missense_variant Exon 2 of 2 2 ENSP00000460659.1 I3L3R1
HOXB8ENST00000498634.2 linkc.172T>C p.Phe58Leu missense_variant Exon 1 of 2 3 ENSP00000460254.1 I3L383
HOXB7ENST00000567101.2 linkn.60-5211T>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151730
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
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
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251480
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461538
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151730
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74078
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Benign
0.93
DEOGEN2
Benign
0.36
T;T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.82
T;T
M_CAP
Uncertain
0.24
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.65
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-3.5
D;.
REVEL
Benign
0.26
Sift
Benign
0.33
T;.
Sift4G
Benign
0.61
T;T
Polyphen
0.16
B;.
Vest4
0.22
MutPred
0.26
Loss of methylation at K209 (P = 0.0557);.;
MVP
0.83
MPC
1.1
ClinPred
0.38
T
GERP RS
2.0
Varity_R
0.44
gMVP
0.63

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: rs553693117; hg19: chr17-46690668; API