17-48610715-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004502.4(HOXB7):​c.204G>C​(p.Gln68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

HOXB7
NM_004502.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.357
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2993799).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXB7NM_004502.4 linkc.204G>C p.Gln68His 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.204G>C p.Gln68His missense_variant Exon 1 of 2 1 NM_004502.4 ENSP00000239165.7 P09629
HOXB7ENST00000567101.2 linkn.60-2620G>C intron_variant Intron 1 of 1 2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.204G>C (p.Q68H) alteration is located in exon 1 (coding exon 1) of the HOXB7 gene. This alteration results from a G to C substitution at nucleotide position 204, causing the glutamine (Q) at amino acid position 68 to be replaced by a histidine (H). 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
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Benign
0.95
DEOGEN2
Benign
0.11
T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
0.76
N
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.44
N
REVEL
Benign
0.094
Sift
Benign
0.30
T
Sift4G
Benign
0.51
T
Polyphen
0.99
D
Vest4
0.35
MutPred
0.46
Loss of disorder (P = 0.1977);
MVP
0.52
MPC
0.53
ClinPred
0.46
T
GERP RS
3.3
Varity_R
0.063
gMVP
0.57

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: rs1335616544; hg19: chr17-46688077; API