17-48610581-T-A

Variant names:

• chr17-48610581-T-A
• rs751919858
• NM_004502.4:c.338A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004502.4(HOXB7):​c.338A>T​(p.Gln113Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q113R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: HOXB7 NM_004502.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21972892).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004502.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB7	NM_004502.4	MANE Select	c.338A>T	p.Gln113Leu	missense	Exon 1 of 2	NP_004493.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB7	ENST00000239165.9	TSL:1 MANE Select	c.338A>T	p.Gln113Leu	missense	Exon 1 of 2	ENSP00000239165.7	P09629
	HOXB7	ENST00000567101.2	TSL:2	n.60-2486A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396850 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688892

African (AFR) AF: 0.00 AC: 0 AN: 31440

American (AMR) AF: 0.00 AC: 0 AN: 35640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35744

South Asian (SAS) AF: 0.00 AC: 0 AN: 79476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5564

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077850

Other (OTH) AF: 0.00 AC: 0 AN: 57780

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.082
Eigen_PC	Benign	0.032
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.022	D
MutationAssessor	Benign	1.6	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.31
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.47		Loss of methylation at K111 (P = 0.0876)
MVP		0.91
MPC		0.54
ClinPred		0.42	T
GERP RS		3.9
PromoterAI		0.0036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.38
gMVP		0.46

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

Other links and lift over

dbSNP: rs751919858; hg19: chr17-46687943;