17-48610762-C-A

Variant names:

• chr17-48610762-C-A
• rs1330282869
• NM_004502.4:c.157G>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004502.4(HOXB7):​c.157G>T​(p.Ala53Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,445,406 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: HOXB7 NM_004502.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.582

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11133665).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXB7	NM_004502.4	c.157G>T	p.Ala53Ser	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.157G>T	p.Ala53Ser	missense_variant	Exon 1 of 2	1	NM_004502.4	ENSP00000239165.7
HOXB7	ENST00000567101.2	n.60-2667G>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000104 AC: 15 AN: 1445406 Hom.: 0 Cov.: 31 AF XY: 0.00000837 AC XY: 6 AN XY: 717264

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000236

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: 0.0000118

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.157G>T (p.A53S) alteration is located in exon 1 (coding exon 1) of the HOXB7 gene. This alteration results from a G to T substitution at nucleotide position 157, causing the alanine (A) at amino acid position 53 to be replaced by a serine (S). 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	0.065
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.65	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.063
Sift	Benign	0.90	T
Sift4G	Benign	0.90	T
Polyphen		0.038	B
Vest4		0.17
MutPred		0.34		Gain of catalytic residue at A53 (P = 0.0416);
MVP		0.27
MPC		0.52
ClinPred		0.20	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.33

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: rs1330282869; hg19: chr17-46688124;