chr17-48580565-G-A

Variant names:

• chr17-48580565-G-A
• rs3809782
• NM_001384749.1:c.-424-6551C>T

Variant summary

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

The NM_001384749.1(HOXB3):​c.-424-6551C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,688 control chromosomes in the GnomAD database, including 29,802 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 0.62 (29793 hom., cov: 29)
  • Exomes 𝑓: 0.77 (9 hom.)
• Consequence: HOXB3 NM_001384749.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 9 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]

ENSG00000257178 (HGNC:):

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=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.-424-6551C>T		intron	N/A	NP_001371678.1
	HOXBLINC	NR_183916.2		n.4360C>T		non_coding_transcript_exon	Exon 1 of 1
	HOXB3	NM_001384747.1		c.-14+9560C>T		intron	N/A	NP_001371676.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXB3	ENST00000498678.6	TSL:2 MANE Select	c.-424-6551C>T		intron	N/A	ENSP00000420595.1
	HOXB3	ENST00000476342.1	TSL:1	c.-14+9560C>T		intron	N/A	ENSP00000418892.1
	ENSG00000257178	ENST00000548801.1	TSL:6	n.1695C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94661 AN: 151544 Hom.: 29778 Cov.: 29

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.769 AC: 20 AN: 26 Hom.: 9 Cov.: 0 AF XY: 0.667 AC XY: 12 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.900 AC: 18 AN: 20

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.624 AC: 94712 AN: 151662 Hom.: 29793 Cov.: 29 AF XY: 0.623 AC XY: 46180 AN XY: 74114

African (AFR) AF: 0.544 AC: 22456 AN: 41282

American (AMR) AF: 0.638 AC: 9733 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2230 AN: 3466

East Asian (EAS) AF: 0.752 AC: 3869 AN: 5142

South Asian (SAS) AF: 0.557 AC: 2674 AN: 4804

European-Finnish (FIN) AF: 0.658 AC: 6919 AN: 10512

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44746 AN: 67886

Other (OTH) AF: 0.655 AC: 1380 AN: 2106

Alfa AF: 0.651 Hom.: 124916

Bravo AF: 0.624

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		1.0
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: rs3809782; hg19: chr17-46657927;