17-48610715-C-G

Variant names:

• chr17-48610715-C-G
• rs1335616544
• NM_004502.4:c.204G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.357

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]

ACMG classification

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
HOXB7	NM_004502.4	c.204G>C	p.Gln68His	missense_variant	Exon 1 of 2	ENST00000239165.9	NP_004493.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB7	ENST00000239165.9	c.204G>C	p.Gln68His	missense_variant	Exon 1 of 2	1	NM_004502.4	ENSP00000239165.7
HOXB7	ENST00000567101.2	n.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

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

Other links and lift over

dbSNP: rs1335616544; hg19: chr17-46688077;