NM_004502.4:c.349G>T

Variant names:

• chr17-48610570-C-A
• NM_004502.4:c.349G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004502.4(HOXB7):​c.349G>T​(p.Asp117Tyr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXB7 NM_004502.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35720402).

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.349G>T	p.Asp117Tyr	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.349G>T	p.Asp117Tyr	missense	Exon 1 of 2	ENSP00000239165.7	P09629
	HOXB7	ENST00000567101.2	TSL:2	n.60-2475G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1385486 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 682206

African (AFR) AF: 0.00 AC: 0 AN: 30864

American (AMR) AF: 0.00 AC: 0 AN: 33460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24738

East Asian (EAS) AF: 0.00 AC: 0 AN: 35162

South Asian (SAS) AF: 0.00 AC: 0 AN: 78606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071926

Other (OTH) AF: 0.00 AC: 0 AN: 57236

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.099
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	2.0	M
PhyloP100		1.4
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.48
Sift	Benign	0.11	T
Sift4G	Uncertain	0.042	D
Polyphen		0.53	P
Vest4		0.42
MutPred		0.49		Gain of phosphorylation at D117 (P = 0.0166)
MVP		0.92
MPC		0.95
ClinPred		0.68	D
GERP RS		3.9
PromoterAI		-0.065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.21
gMVP		0.58

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

hg19: chr17-46687932;