rs144625073

Variant summary

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

The NM_002144.4(HOXB1):ā€‹c.484G>Cā€‹(p.Glu162Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,972 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000099 ( 0 hom., cov: 32)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

HOXB1
NM_002144.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62
Variant links:
Genes affected
HOXB1 (HGNC:5111): (homeobox B1) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXB genes located in a cluster on chromosome 17. [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=0.08045408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB1NM_002144.4 linkc.484G>C p.Glu162Gln missense_variant Exon 1 of 2 ENST00000239174.7 NP_002135.2 P14653-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXB1ENST00000239174.7 linkc.484G>C p.Glu162Gln missense_variant Exon 1 of 2 1 NM_002144.4 ENSP00000355140.5 P14653-1
HOXB1ENST00000577092.1 linkc.484G>C p.Glu162Gln missense_variant Exon 1 of 1 6 ENSP00000459066.1 P14653-2

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152106
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000362
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:
0.0000318
AC:
8
AN:
251382
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.000431
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461866
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152106
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.000362
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
Alfa
AF:
0.0000217
Hom.:
0
Bravo
AF:
0.000106
ExAC
AF:
0.0000494
AC:
6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.070
T;T;.
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.73
.;T;T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.080
T;T;T
MetaSVM
Uncertain
-0.029
T
MutationAssessor
Benign
1.2
L;L;L
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-0.030
N;.;.
REVEL
Benign
0.20
Sift
Benign
0.41
T;.;.
Sift4G
Benign
0.47
T;.;T
Polyphen
0.98
D;D;.
Vest4
0.14
MutPred
0.24
Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);Loss of solvent accessibility (P = 0.0721);
MVP
0.93
MPC
1.1
ClinPred
0.11
T
GERP RS
3.5
Varity_R
0.14
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs144625073; hg19: chr17-46607783; API