chr17-48557657-C-T

Position:

• chr17-48557657-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384749.1(HOXB3):​c.-246-2039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 151,886 control chromosomes in the GnomAD database, including 24,312 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 0.56 (24312 hom., cov: 30)
• Consequence: HOXB3 NM_001384749.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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-AS2 (HGNC:40284): (HOXB cluster antisense RNA 2)

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB3	NM_001384749.1	c.-246-2039G>A		intron_variant		ENST00000498678.6	NP_001371678.1
HOXB-AS2	NR_046610.1	n.1202+299C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB3	ENST00000498678.6	c.-246-2039G>A		intron_variant		2	NM_001384749.1	ENSP00000420595	P1
HOXB-AS2	ENST00000464382.2	n.97+299C>T		intron_variant, non_coding_transcript_variant		4
HOXB-AS3	ENST00000465846.6	n.77+7711C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84458 AN: 151768 Hom.: 24297 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.556 AC: 84505 AN: 151886 Hom.: 24312 Cov.: 30 AF XY: 0.555 AC XY: 41210 AN XY: 74188

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.604

Alfa AF: 0.594 Hom.: 3240

Bravo AF: 0.549

Asia WGS AF: 0.510 AC: 1774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.2
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4793927; hg19: chr17-46635019;