chr17-48567315-C-T

Variant names:

• chr17-48567315-C-T
• rs9906289
• NM_001384749.1:c.-247+6522G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384749.1(HOXB3):​c.-247+6522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,256 control chromosomes in the GnomAD database, including 324 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.057 (324 hom., cov: 32)
• Consequence: HOXB3 NM_001384749.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 7 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-AS3 (HGNC:40283): (HOXB cluster antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0997 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	NM_001384749.1	MANE Select	c.-247+6522G>A		intron	N/A	NP_001371678.1
	HOXB3	NM_001384747.1		c.-13-14828G>A		intron	N/A	NP_001371676.1
	HOXB3	NM_002146.4		c.-247+6522G>A		intron	N/A	NP_002137.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.-247+6522G>A		intron	N/A	ENSP00000420595.1
	HOXB3	ENST00000311626.8	TSL:1	c.-247+6522G>A		intron	N/A	ENSP00000308252.4
	HOXB3	ENST00000476342.1	TSL:1	c.-13-14828G>A		intron	N/A	ENSP00000418892.1

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8750 AN: 152138 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.0118

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0703

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0575 AC: 8754 AN: 152256 Hom.: 324 Cov.: 32 AF XY: 0.0555 AC XY: 4132 AN XY: 74446

African (AFR) AF: 0.102 AC: 4247 AN: 41528

American (AMR) AF: 0.0490 AC: 750 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 169 AN: 3472

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5178

South Asian (SAS) AF: 0.0220 AC: 106 AN: 4826

European-Finnish (FIN) AF: 0.0118 AC: 125 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3066 AN: 68024

Other (OTH) AF: 0.0691 AC: 146 AN: 2112

Alfa AF: 0.0480 Hom.: 405

Bravo AF: 0.0628

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.81
DANN	Benign	0.87
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs9906289; hg19: chr17-46644677;