17-48530596-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002144.4(HOXB1):​c.309A>T​(p.Gln103His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,613,906 control chromosomes in the GnomAD database, including 27,379 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2043 hom., cov: 32)
Exomes 𝑓: 0.18 ( 25336 hom. )

Consequence

HOXB1
NM_002144.4 missense

Scores

2
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

Publications

37 publications found
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]
HOXB1 Gene-Disease associations (from GenCC):
  • facial paresis, hereditary congenital, 3
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
  • congenital hereditary facial paralysis-variable hearing loss syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0011953115).
BP6
Variant 17-48530596-T-A is Benign according to our data. Variant chr17-48530596-T-A is described in ClinVar as [Benign]. Clinvar id is 1239766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB1NM_002144.4 linkc.309A>T p.Gln103His 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.309A>T p.Gln103His missense_variant Exon 1 of 2 1 NM_002144.4 ENSP00000355140.5 P14653-1
HOXB1ENST00000577092.1 linkc.309A>T p.Gln103His missense_variant Exon 1 of 1 6 ENSP00000459066.1 P14653-2
ENSG00000294508ENST00000724000.1 linkn.817+2223T>A intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.153
AC:
23256
AN:
152076
Hom.:
2042
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0749
Gnomad AMI
AF:
0.295
Gnomad AMR
AF:
0.135
Gnomad ASJ
AF:
0.183
Gnomad EAS
AF:
0.0881
Gnomad SAS
AF:
0.132
Gnomad FIN
AF:
0.223
Gnomad MID
AF:
0.171
Gnomad NFE
AF:
0.196
Gnomad OTH
AF:
0.166
GnomAD2 exomes
AF:
0.161
AC:
40355
AN:
250544
AF XY:
0.163
show subpopulations
Gnomad AFR exome
AF:
0.0733
Gnomad AMR exome
AF:
0.110
Gnomad ASJ exome
AF:
0.190
Gnomad EAS exome
AF:
0.0889
Gnomad FIN exome
AF:
0.222
Gnomad NFE exome
AF:
0.196
Gnomad OTH exome
AF:
0.178
GnomAD4 exome
AF:
0.182
AC:
266168
AN:
1461712
Hom.:
25336
Cov.:
33
AF XY:
0.181
AC XY:
131342
AN XY:
727164
show subpopulations
African (AFR)
AF:
0.0718
AC:
2403
AN:
33478
American (AMR)
AF:
0.113
AC:
5048
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.194
AC:
5057
AN:
26134
East Asian (EAS)
AF:
0.0575
AC:
2284
AN:
39700
South Asian (SAS)
AF:
0.124
AC:
10706
AN:
86256
European-Finnish (FIN)
AF:
0.221
AC:
11796
AN:
53306
Middle Eastern (MID)
AF:
0.142
AC:
818
AN:
5768
European-Non Finnish (NFE)
AF:
0.196
AC:
217531
AN:
1111962
Other (OTH)
AF:
0.174
AC:
10525
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
13752
27504
41255
55007
68759
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
7468
14936
22404
29872
37340
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.153
AC:
23258
AN:
152194
Hom.:
2043
Cov.:
32
AF XY:
0.153
AC XY:
11384
AN XY:
74400
show subpopulations
African (AFR)
AF:
0.0749
AC:
3114
AN:
41560
American (AMR)
AF:
0.135
AC:
2068
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.183
AC:
634
AN:
3472
East Asian (EAS)
AF:
0.0878
AC:
452
AN:
5150
South Asian (SAS)
AF:
0.132
AC:
640
AN:
4832
European-Finnish (FIN)
AF:
0.223
AC:
2367
AN:
10602
Middle Eastern (MID)
AF:
0.173
AC:
51
AN:
294
European-Non Finnish (NFE)
AF:
0.196
AC:
13320
AN:
67972
Other (OTH)
AF:
0.163
AC:
343
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.511
Heterozygous variant carriers
0
1041
2083
3124
4166
5207
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
252
504
756
1008
1260
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.171
Hom.:
1858
Bravo
AF:
0.142
TwinsUK
AF:
0.203
AC:
751
ALSPAC
AF:
0.187
AC:
721
ESP6500AA
AF:
0.0778
AC:
343
ESP6500EA
AF:
0.188
AC:
1621
ExAC
AF:
0.161
AC:
19528
Asia WGS
AF:
0.131
AC:
455
AN:
3478
EpiCase
AF:
0.195
EpiControl
AF:
0.194

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Jun 09, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
5.4
DANN
Benign
0.83
DEOGEN2
Benign
0.22
T;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.059
N
LIST_S2
Benign
0.45
.;T;T
MetaRNN
Benign
0.0012
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.8
L;L;L
PhyloP100
-1.4
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-2.3
N;.;.
REVEL
Uncertain
0.36
Sift
Uncertain
0.015
D;.;.
Sift4G
Benign
0.077
T;.;D
Polyphen
0.64
P;P;.
Vest4
0.26
MutPred
0.10
Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);Gain of catalytic residue at Q103 (P = 0.0787);
MPC
0.71
ClinPred
0.030
T
GERP RS
-5.7
PromoterAI
-0.0078
Neutral
Varity_R
0.13
gMVP
0.48
Mutation Taster
=99/1
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12939811; hg19: chr17-46607958; COSMIC: COSV53316862; API