rs3809782

chr17-48580565-G-Achr17-48580565-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXB3	NM_001384749.1	c.-424-6551C>T		intron_variant		ENST00000498678.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXB3	ENST00000498678.6	c.-424-6551C>T		intron_variant		2	NM_001384749.1	P1
	ENST00000548801.1	n.1695C>T		non_coding_transcript_exon_variant	1/1
HOXB-AS3	ENST00000465846.6	n.78-19882G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 1.00

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

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.655

Alfa AF: 0.659 Hom.: 55347

Bravo AF: 0.624

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809782; hg19: chr17-46657927;