Variant 17-48579816-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384749.1(HOXB3):c.-424-5802T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 457,800 control chromosomes in the GnomAD database, including 343 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 0.019 ( 87 hom., cov: 31)

Exomes 𝑓: 0.020 ( 256 hom. )

Consequence

HOXB3
NM_001384749.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0610

Variant links:

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]

HOXB3 links:

(HGNC:):

links:

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

HOXB-AS3 links:

MIR10A (HGNC:31497): (microRNA 10a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR10A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXB3	NM_001384749.1 linkuse as main transcript	c.-424-5802T>A		intron_variant		ENST00000498678.6	NP_001371678.1
MIR10A	NR_029608.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXB3	ENST00000498678.6 linkuse as main transcript	c.-424-5802T>A	intron_variant		2	NM_001384749.1	ENSP00000420595	P1	P14651-1
	ENST00000548801.1 linkuse as main transcript	n.2444T>A	non_coding_transcript_exon_variant	1/1
HOXB-AS3	ENST00000465846.6 linkuse as main transcript	n.78-20631A>T	intron_variant, non_coding_transcript_variant		3
MIR10A	ENST00000385043.1 linkuse as main transcript		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2830

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.00378

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00560

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0286

AC:

4869

AN:

170352

Hom.:

237

AF XY:

0.0245

AC XY:

2307

AN XY:

94244

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.00252

Gnomad EAS exome

AF:

0.0674

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.00457

Gnomad NFE exome

AF:

0.00638

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0201

AC:

6136

AN:

305594

Hom.:

256

Cov.:

AF XY:

0.0185

AC XY:

3260

AN XY:

175766

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.00247

Gnomad4 EAS exome

AF:

0.0685

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.00439

Gnomad4 NFE exome

AF:

0.00619

Gnomad4 OTH exome

AF:

0.0142

GnomAD4 genome

AF:

0.0187

AC:

2842

AN:

152206

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1490

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.0753

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0661

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.00378

Gnomad4 NFE

AF:

0.00562

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.0

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over