rs747283545

Variant names:

• chr17-48550756-G-T
• rs747283545
• NM_001384749.1:c.874C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-48550756-G-T
• chr17-48550756-G-A
• chr17-48550756-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001384749.1(HOXB3):​c.874C>A​(p.Pro292Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,596,264 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P292R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: HOXB3 NM_001384749.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

Genes affected

HOXB3 (HGNC:5114): (homeobox B3) This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

HOXB-AS1 (HGNC:43744): (HOXB cluster antisense RNA 1)

HOXB-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384749.1. 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
	HOXB3	NM_001384749.1	MANE Select	c.874C>A	p.Pro292Thr	missense	Exon 5 of 5	NP_001371678.1	P14651-1
	HOXB3	NM_001384747.1		c.874C>A	p.Pro292Thr	missense	Exon 3 of 3	NP_001371676.1	P14651-1
	HOXB3	NM_002146.4		c.874C>A	p.Pro292Thr	missense	Exon 4 of 4	NP_002137.4	B3KNJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.874C>A	p.Pro292Thr	missense	Exon 5 of 5	ENSP00000420595.1	P14651-1
	HOXB3	ENST00000311626.8	TSL:1	c.874C>A	p.Pro292Thr	missense	Exon 4 of 4	ENSP00000308252.4	P14651-1
	HOXB3	ENST00000470495.1	TSL:1	c.874C>A	p.Pro292Thr	missense	Exon 2 of 2	ENSP00000417207.1	P14651-1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000290 AC: 7 AN: 241736 AF XY: 0.0000306

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000639

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000111 AC: 16 AN: 1444160 Hom.: 0 Cov.: 32 AF XY: 0.0000154 AC XY: 11 AN XY: 715766

African (AFR) AF: 0.00 AC: 0 AN: 33062

American (AMR) AF: 0.00 AC: 0 AN: 43554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1100692

Other (OTH) AF: 0.0000168 AC: 1 AN: 59528

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152104 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Benign	1.0	L
PhyloP100		4.5
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.49
Sift	Benign	0.31	T
Sift4G	Benign	0.23	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.14		Gain of glycosylation at P292 (P = 0.0595)
MVP		0.75
MPC		0.94
ClinPred		0.51	D
GERP RS		3.8
Varity_R		0.43
gMVP		0.67
Mutation Taster		=30/70	disease causing

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: rs747283545; hg19: chr17-46628118;