17-48610702-C-T

Variant summary

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

The NM_004502.4(HOXB7):​c.217G>A​(p.Val73Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,354 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

HOXB7
NM_004502.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.616
Variant links:
Genes affected
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=0.21293142).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB7NM_004502.4 linkc.217G>A p.Val73Ile missense_variant Exon 1 of 2 ENST00000239165.9 NP_004493.3 P09629

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXB7ENST00000239165.9 linkc.217G>A p.Val73Ile missense_variant Exon 1 of 2 1 NM_004502.4 ENSP00000239165.7 P09629
HOXB7ENST00000567101.2 linkn.60-2607G>A intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
7.01e-7
AC:
1
AN:
1426354
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
707392
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.13e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.217G>A (p.V73I) alteration is located in exon 1 (coding exon 1) of the HOXB7 gene. This alteration results from a G to A substitution at nucleotide position 217, causing the valine (V) at amino acid position 73 to be replaced by an isoleucine (I). 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
0.086
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.0019
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.24
N
REVEL
Benign
0.042
Sift
Benign
0.26
T
Sift4G
Benign
0.19
T
Polyphen
0.27
B
Vest4
0.27
MutPred
0.57
Loss of phosphorylation at Y74 (P = 0.1452);
MVP
0.40
MPC
0.49
ClinPred
0.61
D
GERP RS
4.3
Varity_R
0.057
gMVP
0.25

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: chr17-46688064; API