17-48579816-A-T

Variant names:

• chr17-48579816-A-T
• rs3809783
• NM_001384749.1:c.-424-5802T>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.-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610
• Publications: 11 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)

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HOXB3	NM_001384749.1	c.-424-5802T>A		intron_variant	Intron 1 of 4	ENST00000498678.6	NP_001371678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXB3	ENST00000498678.6	c.-424-5802T>A		intron_variant	Intron 1 of 4	2	NM_001384749.1	ENSP00000420595.1

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2830 AN: 152088 Hom.: 84 Cov.: 31

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

GnomAD2 exomes AF: 0.0286 AC: 4869 AN: 170352 AF XY: 0.0245

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 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.: 0 AF XY: 0.0185 AC XY: 3260 AN XY: 175766

African (AFR) AF: 0.0172 AC: 100 AN: 5808

American (AMR) AF: 0.127 AC: 2900 AN: 22890

Ashkenazi Jewish (ASJ) AF: 0.00247 AC: 24 AN: 9710

East Asian (EAS) AF: 0.0685 AC: 639 AN: 9330

South Asian (SAS) AF: 0.0211 AC: 1153 AN: 54516

European-Finnish (FIN) AF: 0.00439 AC: 128 AN: 29152

Middle Eastern (MID) AF: 0.0117 AC: 19 AN: 1624

European-Non Finnish (NFE) AF: 0.00619 AC: 987 AN: 159424

Other (OTH) AF: 0.0142 AC: 186 AN: 13140

GnomAD4 genome AF: 0.0187 AC: 2842 AN: 152206 Hom.: 87 Cov.: 31 AF XY: 0.0200 AC XY: 1490 AN XY: 74418

African (AFR) AF: 0.0190 AC: 789 AN: 41526

American (AMR) AF: 0.0753 AC: 1152 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.0661 AC: 343 AN: 5186

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4822

European-Finnish (FIN) AF: 0.00378 AC: 40 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00562 AC: 382 AN: 68002

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.0113 Hom.: 8

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
PhyloP100		0.061
PromoterAI		0.0088	Neutral
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: rs3809783; hg19: chr17-46657178; COSMIC: COSV60177939; COSMIC: COSV60177939;